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Clinical and Developmental Immunology
Volume 2013 (2013), Article ID 210506, 15 pages
http://dx.doi.org/10.1155/2013/210506
Review Article

Transplant Tolerance: New Insights and Strategies for Long-Term Allograft Acceptance

1Departamento de Biologia, Facultad de Ciencias, Universidad de Chile, 7800024 Santiago, Chile
2Programa de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, 8380453 Santiago, Chile
3Fundacion Ciencia y Vida, 7780272 Santiago, Chile
4Facultad de Ciencias Biologicas, Universidad Andres Bello, 8370146 Santiago, Chile

Received 30 January 2013; Revised 12 April 2013; Accepted 13 April 2013

Academic Editor: Nicolaus Kroger

Copyright © 2013 Paulina Ruiz et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. E. Murray, “Human organ transplantation: background and consequences,” Science, vol. 256, no. 5062, pp. 1411–1416, 1992. View at Google Scholar · View at Scopus
  2. T. Gibson and P. B. Medawar, “The fate of skin homografts in man,” Journal of Anatomy, vol. 77, part 4, pp. 299–310, 1943. View at Google Scholar
  3. L. Brent, A History of Transplantation Immunology, Academic Press, San Diego, Calif, USA, 1997.
  4. P. B. Medawar, “Tests by tissue culture methods on the nature of immunity to,” The Quarterly Journal of Microscopical Science, vol. 89, no. 3, pp. 239–252, 1948. View at Google Scholar · View at Scopus
  5. P. B. Medawar, “The cultivation of adult mammalian skin epithelium in vitro,” Quarterly Journal of Microscopical Science, vol. 89, part 2, pp. 187–196, 1948. View at Google Scholar
  6. R. E. Billingham, L. Brent, and P. B. Medawar, “Quantitative studies on tissue transplantation immunity. II. The origin, strength and duration of actively and adoptively acquired immunity,” Proceedings of the Royal Society London B, vol. 143, no. 910, pp. 58–80, 1954. View at Google Scholar
  7. W. C. Quinby, “The function of the kidney when deprived of its nerves,” The Journal of Experimental Medicine, vol. 23, no. 4, pp. 535–548, 1916. View at Google Scholar
  8. M. Simonsen, “Biological incompatibility in kidney transplantation in dogs. II. Serological investigations,” Acta Pathologica et Microbiologica Scandinavica, vol. 32, no. 1, pp. 1–35, 1953. View at Google Scholar · View at Scopus
  9. J. E. Murray, S. Lang, B. F. Miller, and G. J. Dammin, “Prolonged functional survival of renal autotransplants in the dog,” Surgery, Gynecology and Obstetrics, vol. 103, no. 1, pp. 15–22, 1956. View at Google Scholar
  10. D. M. Hume, J. P. Merrill, B. F. Miller, and G. W. Thorn, “Experiences with renal homotransplantation in the human: report of nine cases,” The Journal of Clinical Investigation, vol. 34, no. 2, pp. 327–382, 1955. View at Google Scholar · View at Scopus
  11. W. R. Guild, J. H. Harrison, J. P. Merrill, and J. Murray, “Successful homotransplantation of the kidney in an identical twin,” Transactions of the American Clinical and Climatological Association, vol. 67, pp. 167–173, 1955. View at Google Scholar · View at Scopus
  12. J. P. Merrill, J. E. Murray, J. H. Harrison, and W. R. Guild, “Successful homotransplantation of the human kidney between identical twins,” Journal of the American Medical Association, vol. 160, no. 4, pp. 277–282, 1956. View at Google Scholar · View at Scopus
  13. G. J. Dammin, N. P. Couch, and J. E. Murray, “Prolonged survival of skin homografts in uremic patients,” Annals of the New York Academy of Sciences, vol. 64, no. 5, pp. 967–976, 1957. View at Google Scholar · View at Scopus
  14. N. P. Couch, J. E. Murray, G. J. Dammin, and L. P. Thomas, “The fate of the skin homograft in the chronically uremic patient,” Surgical Forum, vol. 7, pp. 626–631, 1957. View at Google Scholar · View at Scopus
  15. R. E. Wilson, J. B. Dealy, N. L. Sadowsky, J. M. Corson, and J. E. Murray, “Transplantation of homologous bone marrow and skin from common multiple donors following total body irradiation,” Surgery, vol. 46, no. 1, pp. 261–276, 1959. View at Google Scholar · View at Scopus
  16. J. E. Murray, R. E. Wilson, J. B. Dealy Jr., N. L. Sadowsky, and J. M. Corson, “Fate of skin grafts in irradiated rabbits treated with marrow from single and multiple donors,” Bulletin de la Société Internationale de Chirurgie, vol. 18, no. 4, pp. 364–375, 1959. View at Google Scholar
  17. J. E. Murray, J. P. Merrill, J. H. Harrison, R. E. Wilson, and G. J. Dammin, “Prolonged survival of human-kidney homografts by immunosuppressive drug therapy,” The New England ournal of Medicine, vol. 268, pp. 1315–1323, 1963. View at Google Scholar · View at Scopus
  18. R. Y. Calne, G. P. Alexandre, and J. E. Murray, “A study of the effects of drugs in prolonging survival of homologous renal transplants in dogs,” Annals of the New York Academy of Sciences, vol. 99, pp. 743–761, 1962. View at Google Scholar · View at Scopus
  19. J. P. Merrill, J. E. Murray, F. J. Takacs, E. B. Hager, R. E. Wilson, and G. J. Dammin, “Successful transplantation of kidney from a human cadaver,” The Journal of the American Medical Association, vol. 185, pp. 347–353, 1963. View at Google Scholar · View at Scopus
  20. G. Thiel, F. Harder, and R. Lortscher, “Cyclosporin A used alone or in combination with low-dose steroids in cadaveric renal transplantation,” Klinische Wochenschrift, vol. 61, no. 20, pp. 991–1000, 1983. View at Google Scholar · View at Scopus
  21. D. Tedesco and L. Haragsim, “Cyclosporine: a review,” Journal of Transplantation, vol. 2012, Article ID 230386, 7 pages, 2012. View at Publisher · View at Google Scholar
  22. S. Hariharan, C. P. Johnson, B. A. Bresnahan, S. E. Taranto, M. J. McIntosh, and D. Stablein, “Improved graft survival after renal transplantation in the United States, 1988 to 1996,” The New England Journal of Medicine, vol. 342, no. 9, pp. 605–612, 2000. View at Publisher · View at Google Scholar · View at Scopus
  23. R. Y. Calne and R. Williams, “Liver transplantation in man. I. Observations on technique and organization in five cases,” British Medical Journal, vol. 4, no. 630, pp. 535–540, 1968. View at Google Scholar · View at Scopus
  24. R. Y. Calne, D. B. Evans, B. M. Herbertson et al., “Survival after renal transplantation in man: an interim report on 54 consecutive transplants,” British Medical Journal, vol. 2, no. 602, pp. 404–406, 1968. View at Google Scholar · View at Scopus
  25. R. R. Lower, R. C. Stofer, and N. E. Shumway, “A study of pulmonary valve autotransplantation,” Surgery, vol. 48, no. 6, pp. 1090–1100, 1960. View at Google Scholar · View at Scopus
  26. A. S. Coulson, V. H. Zeitman, and E. B. Stinson, “Immunodepressive serum treatment of acute heart transplant rejection,” British Medical Journal, vol. 1, no. 6012, pp. 749–750, 1976. View at Google Scholar · View at Scopus
  27. H. P. J. Bonarius, F. Baas, E. B. M. Remmerswaal et al., “Monitoring the T-cell receptor repertoire at single-clone resolution,” PLoS ONE, vol. 1, no. 1, article e55, 2006. View at Publisher · View at Google Scholar · View at Scopus
  28. H. von Boehmer, I. Aifantis, F. Gounari et al., “Thymic selection revisited: how essential is it?” Immunological Reviews, vol. 191, pp. 62–78, 2003. View at Publisher · View at Google Scholar · View at Scopus
  29. A. D. Griesemer, E. C. Sorenson, and M. A. Hardy, “The role of the thymus in tolerance,” Transplantation, vol. 90, no. 5, pp. 465–474, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. C. D. Surh and J. Sprent, “T-cell apoptosis detected in situ during positive and negative selection in the thymus,” Nature, vol. 372, no. 6501, pp. 100–103, 1994. View at Publisher · View at Google Scholar · View at Scopus
  31. M. Egerton, R. Scollay, and K. Shortman, “Kinetics of mature T-cell development in the thymus,” Proceedings of the National Academy of Sciences of the United States of America, vol. 87, no. 7, pp. 2579–2582, 1990. View at Google Scholar · View at Scopus
  32. Y. Takahama, “Journey through the thymus: stromal guides for T-cell development and selection,” Nature Reviews Immunology, vol. 6, no. 2, pp. 127–135, 2006. View at Publisher · View at Google Scholar · View at Scopus
  33. J. G. Cyster, “Settling the thymus: immigration requirements,” Journal of Experimental Medicine, vol. 206, no. 4, pp. 731–734, 2009. View at Publisher · View at Google Scholar · View at Scopus
  34. J. Perheentupa, “Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy,” Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 8, pp. 2843–2850, 2006. View at Publisher · View at Google Scholar · View at Scopus
  35. P. Peterson and L. Peltonen, “Autoimmune polyendocrinopathy syndrome type 1 (APS1) and AIRE gene: new views on molecular basis of autoimmunity,” Journal of Autoimmunity, vol. 25, pp. 49–55, 2005. View at Publisher · View at Google Scholar · View at Scopus
  36. N. Kuroda, T. Mitani, N. Takeda et al., “Development of autoimmunity against transcriptionally unrepressed target antigen in the thymus of Aire-deficient mice,” Journal of Immunology, vol. 174, no. 4, pp. 1862–1870, 2005. View at Google Scholar · View at Scopus
  37. C. Ramsey, O. Winqvist, L. Puhakka et al., “Aire deficient mice develop multiple features of APECED phenotype and show altered immune response,” Human Molecular Genetics, vol. 11, no. 4, pp. 397–409, 2002. View at Google Scholar · View at Scopus
  38. T. C. Metzger and M. S. Anderson, “Control of central and peripheral tolerance by Aire,” Immunological Reviews, vol. 241, no. 1, pp. 89–103, 2011. View at Publisher · View at Google Scholar · View at Scopus
  39. D. L. Mueller, “Mechanisms maintaining peripheral tolerance,” Nature Immunology, vol. 11, no. 1, pp. 21–27, 2010. View at Publisher · View at Google Scholar · View at Scopus
  40. G. Y. Liu, P. J. Fairchild, R. M. Smith, J. R. Prowle, D. Kioussis, and D. C. Wraith, “Low avidity recognition of self-antigen by T cells permits escape from central tolerance,” Immunity, vol. 3, no. 4, pp. 407–415, 1995. View at Google Scholar · View at Scopus
  41. C. Bouneaud, P. Kourilsky, and P. Bousso, “Impact of negative selection on the T cell repertoire reactive to a self-peptide: a large fraction of T cell clones escapes clonal deletion,” Immunity, vol. 13, no. 6, pp. 829–840, 2000. View at Publisher · View at Google Scholar · View at Scopus
  42. J. Goverman, A. Woods, L. Larson, L. P. Weiner, L. Hood, and D. M. Zaller, “Transgenic mice that express a myelin basic protein-specific T cell receptor develop spontaneous autoimmunity,” Cell, vol. 72, no. 4, pp. 551–560, 1993. View at Publisher · View at Google Scholar · View at Scopus
  43. T. Bianchi, L. B. Pincus, M. A. Wurbel et al., “Maintenance of peripheral tolerance through controlled tissue homing of antigen-specific T cells in K14-mOVA mice,” Journal of Immunology, vol. 182, no. 8, pp. 4665–4674, 2009. View at Publisher · View at Google Scholar · View at Scopus
  44. K. J. Wood and S. Sakaguchi, “Regulatory T cells in transplantation tolerance,” Nature Reviews Immunology, vol. 3, no. 3, pp. 199–210, 2003. View at Publisher · View at Google Scholar · View at Scopus
  45. A. M. Thornton and E. M. Shevach, “CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production,” Journal of Experimental Medicine, vol. 188, no. 2, pp. 287–296, 1998. View at Publisher · View at Google Scholar · View at Scopus
  46. C. A. Piccirillo and E. M. Shevach, “Cutting edge: control of CD8+ T cell activation by CD4+CD25+ immunoregulatory cells,” Journal of Immunology, vol. 167, no. 3, pp. 1137–1140, 2001. View at Google Scholar · View at Scopus
  47. M. Skoberne, A.-S. Beignon, M. Larsson, and N. Bhardwaj, “Apoptotic cells at the crossroads of tolerance and immunity,” Current Topics in Microbiology and Immunology, vol. 289, pp. 259–292, 2005. View at Google Scholar
  48. N. Singh, J. Pirsch, and M. Samaniego, “Antibody-mediated rejection: treatment alternatives and outcomes,” Transplantation Reviews, vol. 23, no. 1, pp. 34–46, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. T. Hirohashi, C. M. Chase, P. Della Pelle et al., “A novel pathway of chronic allograft rejection mediated by NK cells and alloantibody,” American Journal of Transplantation, vol. 12, no. 2, pp. 313–321, 2012. View at Publisher · View at Google Scholar
  50. Y. Yamaguchi, “Reviews on mysterious vascular endothelial cells in renal allografts,” Clinical Transplantation, vol. 26, supplement 24, pp. 13–19, 2012. View at Publisher · View at Google Scholar
  51. O. Takeuchi and S. Akira, “Pattern recognition receptors and inflammation,” Cell, vol. 140, no. 6, pp. 805–820, 2010. View at Publisher · View at Google Scholar · View at Scopus
  52. Y. Shi, J. E. Evans, and K. L. Rock, “Molecular identification of a danger signal that alerts the immune system to dying cells,” Nature, vol. 425, no. 6957, pp. 516–521, 2003. View at Publisher · View at Google Scholar · View at Scopus
  53. S. H. Sacks and W. Zhou, “The role of complement in the early immune response to transplantation,” Nature Reviews Immunology, vol. 12, no. 6, pp. 431–442, 2012. View at Google Scholar
  54. K. J. Wood, A. Bushell, and J. Hester, “Regulatory immune cells in transplantation,” Nature Reviews Immunology, vol. 12, no. 6, pp. 417–430, 2012. View at Google Scholar
  55. O. B. Herrera, D. Golshayan, R. Tibbott et al., “A novel pathway of alloantigen presentation by dendritic cells,” Journal of Immunology, vol. 173, no. 8, pp. 4828–4837, 2004. View at Google Scholar · View at Scopus
  56. K. Brown, S. H. Sacks, and W. Wong, “Coexpression of donor peptide/recipient MHC complex and intact donor MHC: evidence for a link between the direct and indirect pathways,” American Journal of Transplantation, vol. 11, no. 4, pp. 826–831, 2011. View at Publisher · View at Google Scholar · View at Scopus
  57. B. Afzali, R. I. Lechler, and M. P. Hernandez-Fuentes, “Allorecognition and the alloresponse: clinical implications,” Tissue Antigens, vol. 69, no. 6, pp. 545–556, 2007. View at Publisher · View at Google Scholar · View at Scopus
  58. N. Pilat and T. Wekerle, “Transplantation tolerance through mixed chimerism,” Nature Reviews Nephrology, vol. 6, no. 10, pp. 594–605, 2010. View at Publisher · View at Google Scholar · View at Scopus
  59. T. Fehr and M. Sykes, “Clinical experience with mixed chimerism to induce transplantation tolerance,” Transplant International, vol. 21, no. 12, pp. 1118–1135, 2008. View at Publisher · View at Google Scholar · View at Scopus
  60. S. Janes, P. Dhaliwal, and K. Wood, “Tolerance in renal transplantation: is mixed chimerism the missing link,” Nephrology Dialysis Transplantation, vol. 24, no. 6, pp. 1726–1729, 2009. View at Publisher · View at Google Scholar · View at Scopus
  61. D. H. Sachs, M. Sykes, T. Kawai, and A. B. Cosimi, “Immuno-intervention for the induction of transplantation tolerance through mixed chimerism,” Seminars in Immunology, vol. 23, no. 3, pp. 165–173, 2011. View at Publisher · View at Google Scholar
  62. Y. Tomita, A. Khan, and M. Sykes, “Role of intrathymic clonal deletion and peripheral anergy in transplantation tolerance induced by bone marrow transplantation in mice conditioned with a nonmyeloablative regimen,” Journal of Immunology, vol. 153, no. 3, pp. 1087–1098, 1994. View at Google Scholar · View at Scopus
  63. J. O. Manilay, D. A. Pearson, J. J. Sergio, K. G. Swenson, and M. Sykes, “Intrathymic deletion of alloreactive T cells in mixed bone marrow chimeras prepared with a nonmyeloablative conditioning regimen,” Transplantation, vol. 66, no. 1, pp. 96–102, 1998. View at Publisher · View at Google Scholar · View at Scopus
  64. Y. Tomita, D. H. Sachs, A. Khan, and M. Sykes, “Additional monoclonal antibody (mAB) injections can replace thymic irradiation to allow induction of mixed chimerism and tolerance in mice receiving bone marrow transplantation after conditioning with anti-T cell mABs and 3-GY whole body irradiation,” Transplantation, vol. 61, no. 3, pp. 469–477, 1996. View at Google Scholar · View at Scopus
  65. R. Bonasio, M. L. Scimone, P. Schaerli, N. Grabie, A. H. Lichtman, and U. H. von Andrian, “Clonal deletion of thymocytes by circulating dendritic cells homing to the thymus,” Nature Immunology, vol. 7, no. 10, pp. 1092–1100, 2006. View at Publisher · View at Google Scholar · View at Scopus
  66. B. Dey, M. Sykes, and T. R. Spitzer, “Outcomes of recipients of both bone marrow and solid organ transplants: a review,” Medicine, vol. 77, no. 5, pp. 355–369, 1998. View at Publisher · View at Google Scholar · View at Scopus
  67. C. Helg, B. Chapuis, J. F. Bolle et al., “Renal transplantation without immunosuppression in a host with tolerance induced by allogeneic bone marrow transplantation,” Transplantation, vol. 58, no. 12, pp. 1420–1422, 1994. View at Google Scholar · View at Scopus
  68. M. H. Sayegh, N. A. Fine, J. L. Smith, H. G. Rennke, E. L. Milford, and N. L. Tilney, “Immunologic tolerance to renal allografts after bone marrow transplants from the same donors,” Annals of Internal Medicine, vol. 114, no. 11, pp. 954–955, 1991. View at Google Scholar · View at Scopus
  69. N. Jacobson, E. Taaning, J. Ladefoged, J. K. Kristensen, and F. K. Pedersen, “Tolerance to an HLA-B,DR disparate kidney allograft after bone-marrow transplantation from same donor,” The Lancet, vol. 343, no. 8900, p. 800, 1994. View at Publisher · View at Google Scholar · View at Scopus
  70. H. W. Li and M. Sykes, “Emerging concepts in haematopoietic cell transplantation,” Nature Reviews Immunology, vol. 12, no. 6, pp. 403–416, 2012. View at Google Scholar
  71. Y. Sharabi and D. H. Sachs, “Mixed chimerism and permanent specific transplantation tolerance induced by a nonlethal preparative regimen,” Journal of Experimental Medicine, vol. 169, no. 2, pp. 493–502, 1989. View at Google Scholar · View at Scopus
  72. H. Kohrt and R. Lowsky, “Nonmyeloablative conditioning with total lymphoid irradiation and antithymocyte globulin: an update,” Current Opinion in Hematology, vol. 16, no. 6, pp. 460–465, 2009. View at Publisher · View at Google Scholar · View at Scopus
  73. Y. Sharabi and D. H. Sachs, “Engraftment of allogeneic bone marrow following administration of anti-T cell monoclonal antibodies and low-dose irradiation,” Transplantation Proceedings, vol. 21, no. 1, pp. 233–235, 1989. View at Google Scholar · View at Scopus
  74. L. Stephan, C. Pichavant, M. Bouchentouf et al., “Induction of tolerance across fully mismatched barriers by a nonmyeloablative treatment excluding antibodies or irradiation use,” Cell Transplantation, vol. 15, no. 8-9, pp. 835–846, 2006. View at Google Scholar · View at Scopus
  75. T. Kawai, H. Sogawa, S. Boskovic et al., “CD154 blockade for induction of mixed chimerism and prolonged renal allograft survival in nonhuman primates,” American Journal of Transplantation, vol. 4, no. 9, pp. 1391–1398, 2004. View at Publisher · View at Google Scholar · View at Scopus
  76. T. Wekerle, J. Kurtz, H. Ito et al., “Allogeneic bone marrow transplantation with co-stimulatory blockade induces macrochimerism and tolerance without cytoreductive host treatment,” Nature Medicine, vol. 6, no. 4, pp. 464–469, 2000. View at Publisher · View at Google Scholar · View at Scopus
  77. T. Kawai, A. B. Cosim, T. R. Spitzer et al., “HLA-mismatched renal transplantation without maintenance immunosuppression,” The New England Journal of Medicine, vol. 358, no. 4, pp. 353–361, 2008. View at Publisher · View at Google Scholar
  78. A. B. Adams, M. A. Williams, T. R. Jones et al., “Conferring indirect allospecificity on CD4+CD25+ Tregs by TCR gene transfer favors transplantation tolerance in mice,” The Journal of Clinical Investigation, vol. 111, no. 12, pp. 1887–1895, 2003. View at Google Scholar
  79. Y. Yamada, “Overcoming memory T-cell responses for induction of delayed tolerance in nonhuman primates,” American Journal of Transplantation, vol. 12, no. 2, pp. 330–340, 2012. View at Google Scholar
  80. A. E. Morelli and A. W. Thomson, “Tolerogenic dendritic cells and the quest for transplant tolerance,” Nature Reviews Immunology, vol. 7, no. 8, pp. 610–621, 2007. View at Publisher · View at Google Scholar · View at Scopus
  81. C. van Kooten, G. Lombardi, K. A. Gelderman et al., “Dendritic cells as a tool to induce transplantation tolerance: obstacles and opportunities,” Transplantation, vol. 91, no. 1, pp. 2–7, 2011. View at Publisher · View at Google Scholar · View at Scopus
  82. S. M. Barratt-Boyes and A. W. Thomson, “Dendritic cells: Tools and targets for transplant tolerance,” American Journal of Transplantation, vol. 5, no. 12, pp. 2807–2813, 2005. View at Publisher · View at Google Scholar · View at Scopus
  83. M. Ezzelarab and A. W. Thomson, “Tolerogenic dendritic cells and their role in transplantation,” Seminars in Immunology, vol. 23, no. 4, pp. 252–263, 2011. View at Google Scholar
  84. M. B. Lutz and G. Schuler, “Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity?” Trends in Immunology, vol. 23, no. 9, pp. 445–449, 2002. View at Publisher · View at Google Scholar · View at Scopus
  85. S. J. Divito, Z. Wang, W. J. Shufesky et al., “Endogenous dendritic cells mediate the effects of intravenously injected therapeutic immunosuppressive dendritic cells in transplantation,” Blood, vol. 116, no. 15, pp. 2694–2705, 2010. View at Publisher · View at Google Scholar · View at Scopus
  86. G. Ureta, F. Osorio, J. Morales, M. Rosemblatt, M. R. Bono, and J. A. Fierro, “Generation of dendritic cells with regulatory properties,” Transplantation Proceedings, vol. 39, no. 3, pp. 633–637, 2007. View at Publisher · View at Google Scholar · View at Scopus
  87. H. R. Turnquist, G. Raimondi, A. F. Zahorchak, R. T. Fischer, Z. Wang, and A. W. Thomson, “Rapamycin-conditioned dendritic cells are poor stimulators of allogeneic CD4+ T cells, but enrich for antigen-specific Foxp3+ T regulatory cells and promote organ transplant tolerance,” Journal of Immunology, vol. 178, no. 11, pp. 7018–7031, 2007. View at Google Scholar · View at Scopus
  88. B. T. Fife, I. Guleria, M. G. Bupp et al., “Insulin-induced remission in new-onset NOD mice is maintained by the PD-1-PD-L1 pathway,” Journal of Experimental Medicine, vol. 203, no. 12, pp. 2737–2747, 2006. View at Publisher · View at Google Scholar · View at Scopus
  89. M. E. Keir, S. C. Liang, I. Guleria et al., “Tissue expression of PD-L1 mediates peripheral T cell tolerance,” The Journal of Experimental Medicine, vol. 203, no. 4, pp. 883–895, 2006. View at Google Scholar
  90. M. M. McGrath and N. Najafian, “The role of coinhibitory signaling pathways in transplantation and tolerance,” Frontiers in Immunology, vol. 3, p. 47, 2012. View at Google Scholar
  91. J. Yang, L. V. Riella, S. Chock et al., “The novel costimulatory programmed death ligand 1/B7.1 pathway is functional in inhibiting alloimmune responses in vivo,” The Journal of Immunology, vol. 187, no. 3, pp. 1113–1119, 2011. View at Publisher · View at Google Scholar
  92. I. Puliaeva, K. Soloviova, M. Puliaiev, T. Lang, R. Puliaev, and C. S. Via, “Enhancement of suboptimal CD8 cytotoxic T cell effector function in vivo using antigen-specific CD80 defective T cells,” Journal of Immunology, vol. 186, no. 1, pp. 291–304, 2011. View at Publisher · View at Google Scholar · View at Scopus
  93. J. Hu and Y. Wan, “Tolerogenic dendritic cells and their potential applications,” Immunology, vol. 132, no. 3, pp. 307–314, 2011. View at Publisher · View at Google Scholar · View at Scopus
  94. D. Sauma, A. Fierro, J. R. Mora et al., “Cyclosporine preconditions dendritic cells during differentiation and reduces IL-2 and IL-12 production following activation: a potential tolerogenic effect,” Transplantation Proceedings, vol. 35, no. 7, pp. 2515–2517, 2003. View at Publisher · View at Google Scholar · View at Scopus
  95. A. Fierro, J. R. Mora, M. R. Bono et al., “Dendritic cells and the mode of action of anticalcineurinic drugs: an integrating hypothesis,” Nephrology Dialysis Transplantation, vol. 18, no. 3, pp. 467–468, 2003. View at Publisher · View at Google Scholar · View at Scopus
  96. Y. Y. Lan, Z. Wang, G. Raimondi et al., “‘Alternatively activated’ dendritic cells preferentially secrete IL-10, expand Foxp3+CD4+ T cells, and induce long-term organ allograft survival in combination with CTLA4-Ig,” Journal of Immunology, vol. 177, no. 9, pp. 5868–5877, 2006. View at Google Scholar · View at Scopus
  97. M. B. Lutz, R. M. Suri, M. Niimi et al., “Immature dendritic cells generated with low doses of GM-CSF in the absence of IL-4 are maturation resistant and prolong allograft survival in vivo,” European Journal of Immunology, vol. 30, no. 7, pp. 1813–1822, 2000. View at Google Scholar
  98. F. Salazar-Onfray, J. Charo, M. Petersson et al., “Down-regulation of the expression and function of the transporter associated with antigen processing in murine tumor cell lines expressing IL-10,” Journal of Immunology, vol. 159, no. 7, pp. 3195–3202, 1997. View at Google Scholar · View at Scopus
  99. Z. Qin, G. Noffz, M. Mohaupt, and T. Blankenstein, “Interleukin-10 prevents dendritic cell accumulation and vaccination with granulocyte-macrophage colony-stimulating factor gene-modified tumor cells,” Journal of Immunology, vol. 159, no. 2, pp. 770–776, 1997. View at Google Scholar · View at Scopus
  100. M. E. Keir, M. J. Butte, G. J. Freeman, and A. H. Sharpe, “PD-1 and its ligands in tolerance and immunity,” Annual Review of Immunology, vol. 26, pp. 677–704, 2008. View at Publisher · View at Google Scholar · View at Scopus
  101. R. T. Fischer, H. R. Turnquist, Z. Wang, D. Beer-Stolz, and A. W. Thomson, “Rapamycin-conditioned, alloantigen-pulsed myeloid dendritic cells present donor MHC class I/peptide via the semi-direct pathway and inhibit survival of antigen-specific CD8+ T cells in vitro and in vivo,” Transplant Immunology, vol. 25, no. 1, pp. 20–26, 2011. View at Publisher · View at Google Scholar · View at Scopus
  102. P. Yu, S. Xiong, Q. He et al., “Induction of allogeneic mixed chimerism by immature dendritic cells and bone marrow transplantation leads to prolonged tolerance to major histocompatibility complex disparate allografts,” Immunology, vol. 127, no. 4, pp. 500–511, 2009. View at Publisher · View at Google Scholar · View at Scopus
  103. J. M. Langrehr, D. A. White, R. A. Hoffman, and R. L. Simmons, “Macrophages produce nitric oxide at allograft sites,” Annals of Surgery, vol. 218, no. 2, pp. 159–166, 1993. View at Google Scholar · View at Scopus
  104. W. H. Kitchens, C. M. Chase, S. Uehara et al., “Macrophage depletion suppresses cardiac allograft vasculopathy in mice,” American Journal of Transplantation, vol. 7, no. 12, pp. 2675–2682, 2007. View at Publisher · View at Google Scholar · View at Scopus
  105. S. J. Knechtle, J. D. Pirsch, J. H. Fechner et al., “Campath-1H induction plus rapamycin monotherapy for renal transplantation: results of a pilot study,” American Journal of Transplantation, vol. 3, no. 6, pp. 722–730, 2003. View at Publisher · View at Google Scholar · View at Scopus
  106. X. C. Li, “The significance of non-T-cell pathways in graft rejection: implications for transplant tolerance,” Transplantation, vol. 90, no. 10, pp. 1043–1047, 2010. View at Publisher · View at Google Scholar · View at Scopus
  107. F. S. Sutterwala, G. J. Noel, P. Salgame, and D. M. Mosser, “Reversal of proinflammatory responses by ligating the macrophage Fcγ receptor type I,” Journal of Experimental Medicine, vol. 188, no. 1, pp. 217–222, 1998. View at Publisher · View at Google Scholar · View at Scopus
  108. B. G. Brem-Exner, C. Sattler, J. A. Hutchinson et al., “Macrophages driven to a novel state of activation have anti-inflammatory properties in mice,” Journal of Immunology, vol. 180, no. 1, pp. 335–349, 2008. View at Google Scholar · View at Scopus
  109. D. Hashimoto, A. Chow, M. Greter et al., “Pretransplant CSF-1 therapy expands recipient macrophages and ameliorates GVHD after allogeneic hematopoietic cell transplantation,” Journal of Experimental Medicine, vol. 208, no. 5, pp. 1069–1082, 2011. View at Publisher · View at Google Scholar · View at Scopus
  110. P. Riquelme, S. Tomiuk, A. Kammler et al., “IFN-gamma-induced iNOS expression in mouse regulatory macrophages prolongs allograft survival in fully immunocompetent recipients,” Molecular Therapy, vol. 21, no. 2, pp. 409–422, 2013. View at Google Scholar
  111. J. A. Hutchinson, P. Riquelme, B. Sawitzki et al., “Cutting Edge: immunological consequences and trafficking of human regulatory macrophages administered to renal transplant recipients,” The Journal of Immunology, vol. 187, no. 5, pp. 2072–2078, 2011. View at Google Scholar
  112. H. Pêche, M. Heslan, C. Usal, S. Amigorena, and M. C. Cuturi, “Presentation of donor major histocompatibility complex antigens by bone marrow dendritic cell-derived exosomes modulates allograft rejection,” Transplantation, vol. 76, no. 10, pp. 1503–1510, 2003. View at Publisher · View at Google Scholar · View at Scopus
  113. H. Pêche, K. Renaudin, G. Beriou, E. Merieau, S. Amigorena, and M. C. Cuturi, “Induction of tolerance by exosomes and short-term immunosuppression in a fully MHC-mismatched rat cardiac allograft model,” American Journal of Transplantation, vol. 6, no. 7, pp. 1541–1550, 2006. View at Publisher · View at Google Scholar · View at Scopus
  114. C. Thery, L. Duban, E. Segura, P. Véron, O. Lantz, and S. Amigorena, “Indirect activation of naive CD4+ T cells by dendritic cell-derived exosomes,” Nature Immunology, vol. 3, no. 12, pp. 1156–1162, 2002. View at Google Scholar
  115. E. Segura, C. Nicco, B. Lombard et al., “ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T-cell priming,” Blood, vol. 106, no. 1, pp. 216–223, 2005. View at Publisher · View at Google Scholar · View at Scopus
  116. H. Vincent-Schneider, P. Stumptner-Cuvelette, D. Lankar et al., “Exosomes bearing HLA-DR1 molecules needs dendritic cells to efficiently stimulate specific T cells,” International Immunology, vol. 14, no. 7, pp. 713–722, 2002. View at Google Scholar · View at Scopus
  117. G. J. Wang, Y. Liu, A. Qin et al., “Thymus exosomes-like particles induce regulatory T cells,” Journal of Immunology, vol. 181, no. 8, pp. 5242–5248, 2008. View at Google Scholar · View at Scopus
  118. S. H. Kim, E. R. Lechman, N. Bianco et al., “Exosomes derived from IL-10-treated dendritic cells can suppress inflammation and collagen-induced arthritis,” Journal of Immunology, vol. 174, no. 10, pp. 6440–6448, 2005. View at Google Scholar · View at Scopus
  119. P. P. Singh, C. LeMaire, J. C. Tan, E. Zeng, and J. S. Schorey, “Exosomes released from M. tuberculosis infected cells can suppress ifn-γ mediated activation of naïve macrophages,” PLoS ONE, vol. 6, no. 4, Article ID e18564, 2011. View at Publisher · View at Google Scholar · View at Scopus
  120. C. Théry, A. Regnault, J. Garin et al., “Molecular characterization of dendritic cell-derived exosomes: selective accumulation of the heat shock protein hsc73,” Journal of Cell Biology, vol. 147, no. 3, pp. 599–610, 1999. View at Publisher · View at Google Scholar · View at Scopus
  121. A. E. Morelli, “The immune regulatory effect of apoptotic cells and exosomes on dendritic cells: its impact on transplantation,” American Journal of Transplantation, vol. 6, no. 2, pp. 254–261, 2006. View at Publisher · View at Google Scholar · View at Scopus
  122. B. György, T. G. Szabó, M. Pásztói et al., “Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles,” Cellular and Molecular Life Sciences, vol. 68, no. 16, pp. 2667–2688, 2011. View at Publisher · View at Google Scholar · View at Scopus
  123. H. G. Zhang and W. E. Grizzle, “Exosomes and cancer: a newly described pathway of immune suppression,” Clinical Cancer Research, vol. 17, no. 5, pp. 959–964, 2011. View at Publisher · View at Google Scholar · View at Scopus
  124. M. Desjardins, L. A. Huber, R. G. Parton, and G. Griffiths, “Biogenesis of phagolysosomes proceeds through a sequential series of interactions with the endocytic apparatus,” Journal of Cell Biology, vol. 124, no. 5, pp. 677–688, 1994. View at Google Scholar · View at Scopus
  125. A. E. Morelli and A. T. Larregina, “Apoptotic cell-based therapies against transplant rejection: role of recipient's dendritic cells,” Apoptosis, vol. 15, no. 9, pp. 1083–1097, 2010. View at Publisher · View at Google Scholar · View at Scopus
  126. M. L. Albert, “Death-defying immunity: do apoptotic cells influence antigen processing and presentation?” Nature Reviews Immunology, vol. 4, no. 3, pp. 223–231, 2004. View at Google Scholar · View at Scopus
  127. W. Fiers, R. Beyaert, W. Declercq, and P. Vandenabeele, “More than one way to die: apoptosis, necrosis and reactive oxygen damage,” Oncogene, vol. 18, no. 54, pp. 7719–7730, 1999. View at Google Scholar · View at Scopus
  128. J. H. W. Distler, L. C. Huber, A. J. Hueber et al., “The release of microparticles by apoptotic cells and their effects on macrophages,” Apoptosis, vol. 10, no. 4, pp. 731–741, 2005. View at Publisher · View at Google Scholar · View at Scopus
  129. H. Shimamura, M. Sunamura, K. Tsuchihara, S. Egawa, K. Takeda, and S. Matsuno, “Irradiated pancreatic cancer cells undergo both apoptosis and necrosis, and could be phagocytized by dendritic cells,” European Surgical Research, vol. 37, no. 4, pp. 228–234, 2005. View at Publisher · View at Google Scholar · View at Scopus
  130. V. A. Fadok, D. L. Bratton, and P. M. Henson, “Phagocyte receptors for apoptotic cells: recognition, uptake, and consequences,” Journal of Clinical Investigation, vol. 108, no. 7, pp. 957–962, 2001. View at Publisher · View at Google Scholar · View at Scopus
  131. J. Savill and V. Fadok, “Corpse clearance defines the meaning of cell death,” Nature, vol. 407, no. 6805, pp. 784–788, 2000. View at Publisher · View at Google Scholar · View at Scopus
  132. B. Sauter, M. L. Albert, L. Francisco, M. Larsson, S. Somersan, and N. Bhardwaj, “Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells,” Journal of Experimental Medicine, vol. 191, no. 3, pp. 423–433, 2000. View at Publisher · View at Google Scholar · View at Scopus
  133. W. K. Ip and Y. L. Lau, “Distinct maturation of, but not migration between, human monocyte-derived dendritic cells upon ingestion of apoptotic cells of early or late phases,” Journal of Immunology, vol. 173, no. 1, pp. 189–196, 2004. View at Google Scholar · View at Scopus
  134. A. D. Chernysheva, K. A. Kirou, and M. K. Crow, “T cell proliferation induced by autologous non-T cells is a response to apoptotic cells processed by dendritic cells,” Journal of Immunology, vol. 169, no. 3, pp. 1241–1250, 2002. View at Google Scholar · View at Scopus
  135. M. Škoberne, S. Somersan, W. Almodovar et al., “The apoptotic-cell receptor CR3, but not αvβ5, is a regulator of human dendritic-cell immunostimulatory function,” Blood, vol. 108, no. 3, pp. 947–955, 2006. View at Publisher · View at Google Scholar · View at Scopus
  136. A. Ronchetti, P. Rovere, G. Iezzi et al., “Immunogenicity of apoptotic cells in vivo: role of antigen load, antigen-presenting cells, and cytokines,” Journal of Immunology, vol. 163, no. 1, pp. 130–136, 1999. View at Google Scholar · View at Scopus
  137. W. Chen, M. E. Frank, W. Jin, and S. M. Wahl, “TGF-β released by apoptotic T cells contributes to an immunosuppressive milieu,” Immunity, vol. 14, no. 6, pp. 715–725, 2001. View at Publisher · View at Google Scholar · View at Scopus
  138. H. Feng, Y. Zeng, M. W. Graner, A. Likhacheva, and E. Katsanis, “Exogenous stress proteins enhance the immunogenicity of apoptotic tumor cells and stimulate antitumor immunity,” Blood, vol. 101, no. 1, pp. 245–252, 2003. View at Publisher · View at Google Scholar · View at Scopus
  139. R. M. Steinman, S. Turley, I. Mellman, and K. Inaba, “The induction of tolerance by dendritic cells that have captured apoptotic cells,” Journal of Experimental Medicine, vol. 191, no. 3, pp. 411–416, 2000. View at Publisher · View at Google Scholar · View at Scopus
  140. V. Verhasselt, O. Vosters, C. Beuneu, C. Nicaise, P. Stordeur, and M. Goldman, “Induction of FOXP3-expressing regulatory CD4pos T cells by human mature autologous dendritic cells,” European Journal of Immunology, vol. 34, no. 3, pp. 762–772, 2004. View at Publisher · View at Google Scholar · View at Scopus
  141. R. E. Voll, M. Herrmann, E. A. Roth, C. Stach, J. R. Kalden, and I. Girkontaite, “Immunosuppressive effects of apoptotic cells,” Nature, vol. 390, no. 6658, pp. 350–351, 1997. View at Publisher · View at Google Scholar · View at Scopus
  142. M. Cvetanovic, J. E. Mitchell, V. Patel et al., “Specific recognition of apoptotic cells reveals a ubiquitous and unconventional innate immunity,” Journal of Biological Chemistry, vol. 281, no. 29, pp. 20055–20067, 2006. View at Publisher · View at Google Scholar · View at Scopus
  143. M. A. Gleisner, M. Rosemblatt, J. A. Fierro, and M. R. Bono, “Delivery of alloantigens via apoptotic cells generates dendritic cells with an immature tolerogenic phenotype,” Transplantation Proceedings, vol. 43, no. 6, pp. 2325–2333, 2011. View at Publisher · View at Google Scholar
  144. S. Gallucci, M. Lolkema, and P. Matzinger, “Natural adjuvants: endogenous activators of dendritic cells,” Nature Medicine, vol. 5, no. 11, pp. 1249–1255, 1999. View at Publisher · View at Google Scholar · View at Scopus
  145. L. M. Stuart, M. Lucas, C. Simpson, J. Lamb, J. Savill, and A. Lacy-Hulbert, “Inhibitory effects of apoptotic cell ingestion upon endotoxin-driven myeloid dendritic cell maturation,” Journal of Immunology, vol. 168, no. 4, pp. 1627–1635, 2002. View at Google Scholar · View at Scopus
  146. M. Takahashi and Y. Kobayashi, “Cytokine production in association with phagocytosis of apoptotic cells by immature dendritic cells,” Cellular Immunology, vol. 226, no. 2, pp. 105–115, 2003. View at Publisher · View at Google Scholar · View at Scopus
  147. A. E. Morelli, A. T. Larregina, W. J. Shufesky et al., “Internalization of circulating apoptotic cells by splenic marginal zone dendritic cells: dependence on complement receptors and effect on cytokine production,” Blood, vol. 101, no. 2, pp. 611–620, 2003. View at Publisher · View at Google Scholar · View at Scopus
  148. G. Ren, J. Su, X. Zhao et al., “Apoptotic cells induce immunosuppression through dendritic cells: critical roles of IFN-γ and nitric oxide,” Journal of Immunology, vol. 181, no. 5, pp. 3277–3284, 2008. View at Google Scholar · View at Scopus
  149. C. A. Williams, R. A. Harry, and J. D. McLeod, “Apoptotic cells induce dendritic cell-mediated suppression via interferon-γ-induced IDO,” Immunology, vol. 124, no. 1, pp. 89–101, 2008. View at Publisher · View at Google Scholar · View at Scopus
  150. K. Inaba, S. Turley, F. Yamaide et al., “Efficient presentation of phagocytosed cellular fragments on the major histocompatibility complex class II products of dendritic cells,” Journal of Experimental Medicine, vol. 188, no. 11, pp. 2163–2173, 1998. View at Publisher · View at Google Scholar · View at Scopus
  151. M. L. Albert, B. Sauter, and N. Bhardwaj, “Dendritic cells acquire antigen from apoptotic cells and induce class I- restricted CTLS,” Nature, vol. 392, no. 6671, pp. 86–89, 1998. View at Publisher · View at Google Scholar · View at Scopus
  152. M. L. Albert, S. F. A. Pearce, L. M. Francisco et al., “Immature dendritic cells phagocytose apoptotic cells via αvβ5 and CD36, and cross-present antigens to cytotoxic T lymphocytes,” Journal of Experimental Medicine, vol. 188, no. 7, pp. 1359–1368, 1998. View at Publisher · View at Google Scholar · View at Scopus
  153. T. Iyoda, S. Shimoyama, K. Liu et al., “The CD8+ dendritic cell subset selectively endocytoses dying cells in culture and in vivo,” Journal of Experimental Medicine, vol. 195, no. 10, pp. 1289–1302, 2002. View at Publisher · View at Google Scholar · View at Scopus
  154. B. C. Urban, N. Willcox, and D. J. Roberts, “A role for CD36 in the regulation of dendritic cell function,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 15, pp. 8750–8755, 2001. View at Publisher · View at Google Scholar · View at Scopus
  155. F. P. Huang, N. Platt, M. Wykes et al., “A discrete subpopulation of dendritic cells transports apoptotic intestinal epithelial cells to T cell areas of mesenteric lymph nodes,” Journal of Experimental Medicine, vol. 191, no. 3, pp. 435–443, 2000. View at Publisher · View at Google Scholar · View at Scopus
  156. C. Scheinecker, R. McHugh, E. M. Shevach, and R. N. Germain, “Constitutive presentation of a natural tissue autoantigen exclusively by dendritic cells in the draining lymph node,” Journal of Experimental Medicine, vol. 196, no. 8, pp. 1079–1090, 2002. View at Publisher · View at Google Scholar · View at Scopus
  157. M. De Carvalho Bittencourt, S. Perruche, E. Contassot et al., “Intravenous injection of apoptotic leukocytes enhances bone marrow engraftment across major histocompatibility barriers,” Blood, vol. 98, no. 1, pp. 224–230, 2001. View at Publisher · View at Google Scholar · View at Scopus
  158. I. Verbovetski, H. Bychkov, U. Trahtemberg et al., “Opsonization of apoptotic cells by autologous iC3b facilitates clearance by immature dendritic cells, down-regulates DR and CD86, and up-regulates CC chemokine receptor 7,” Journal of Experimental Medicine, vol. 196, no. 12, pp. 1553–1561, 2002. View at Publisher · View at Google Scholar · View at Scopus
  159. M. Nouri-Shirazi and E. Guinet, “Direct and indirect cross-tolerance of alloreactive T cells by dendritic cells retained in the immature stage,” Transplantation, vol. 74, no. 7, pp. 1035–1044, 2002. View at Google Scholar · View at Scopus
  160. D. L. Xu, Y. Liu, J. M. Tan et al., “Marked prolongation of murine cardiac allograft survival using recipient immature dendritic cells loaded with donor-derived apoptotic cells,” Scandinavian Journal of Immunology, vol. 59, no. 6, pp. 536–544, 2004. View at Publisher · View at Google Scholar · View at Scopus
  161. Z. Wang, A. T. Larregina, W. J. Shufesky et al., “Use of the inhibitory effect of apoptotic cells on dendritic cells for graft survival via T-cell deletion and regulatory T cells,” American Journal of Transplantation, vol. 6, no. 6, pp. 1297–1311, 2006. View at Publisher · View at Google Scholar · View at Scopus
  162. R. I. Lechler, M. Sykes, A. W. Thomson, and L. A. Turka, “Organ transplantation—how much of the promise has been realized?” Nature Medicine, vol. 11, no. 6, pp. 605–613, 2005. View at Publisher · View at Google Scholar · View at Scopus
  163. D. Golshayan, S. Jiang, J. Tsang, M. I. Garin, C. Mottet, and R. I. Lechler, “In vitro-expanded donor alloantigen-specific CD4+CD25+ regulatory T cells promote experimental transplantation tolerance,” Blood, vol. 109, no. 2, pp. 827–835, 2007. View at Publisher · View at Google Scholar · View at Scopus
  164. P. Hoffmann, J. Ermann, M. Edinger, C. Garrison Fathman, and S. Strober, “Donor-type CD4+CD25+ regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation,” Journal of Experimental Medicine, vol. 196, no. 3, pp. 389–399, 2002. View at Publisher · View at Google Scholar · View at Scopus
  165. P. A. Taylor, C. J. Lees, and B. R. Blazar, “The infusion of ex vivo activated and expanded CD4+CD25+ immune regulatory cells inhibits graft-versus-host disease lethality,” Blood, vol. 99, no. 10, pp. 3493–3499, 2002. View at Publisher · View at Google Scholar · View at Scopus
  166. O. Joffre, T. Santolaria, D. Calise et al., “Prevention of acute and chronic allograft rejection with CD4+CD25+Foxp3+ regulatory T lymphocytes,” Nature Medicine, vol. 14, no. 1, pp. 88–92, 2008. View at Publisher · View at Google Scholar · View at Scopus
  167. O. Joffre, N. Gorsse, P. Romagnoli, D. Hudrisier, and J. P. M. Van Meerwijk, “Induction of antigen-specific tolerance to bone marrow allografts with CD4+CD25+ T lymphocytes,” Blood, vol. 103, no. 11, pp. 4216–4221, 2004. View at Publisher · View at Google Scholar · View at Scopus
  168. C. Moore, D. Sauma, P. A. Reyes et al., “Dendritic cells and B cells cooperate in the generation of CD4+CD25+FOXP3+ allogeneic T cells,” Transplantation Proceedings, vol. 42, no. 1, pp. 371–375, 2010. View at Publisher · View at Google Scholar · View at Scopus
  169. C. Moore, D. Sauma, J. Morales, M. R. Bono, M. Rosemblatt, and J. A. Fierro, “Transforming growth factor-β and all-trans retinoic acid generate ex vivo transgenic regulatory T cells with intestinal homing receptors,” Transplantation Proceedings, vol. 41, no. 6, pp. 2670–2672, 2009. View at Publisher · View at Google Scholar · View at Scopus
  170. G. Raimondi, T. L. Sumpter, B. M. Matta et al., “Mammalian target of rapamycin inhibition and alloantigen-specific regulatory T cells synergize to promote long-term graft survival in immunocompetent recipients,” Journal of Immunology, vol. 184, no. 2, pp. 624–636, 2010. View at Publisher · View at Google Scholar · View at Scopus
  171. N. Pilat, C. Klaus, M. Gattringer et al., “Therapeutic efficacy of polyclonal tregs does not require rapamycin in a low-dose irradiation bone marrow transplantation model,” Transplantation, vol. 92, no. 3, pp. 280–288, 2011. View at Publisher · View at Google Scholar · View at Scopus
  172. J. Y. S. Tsang, Y. Tanriver, S. Jiang et al., “Conferring indirect allospecificity on CD4+CD25+ Tregs by TCR gene transfer favors transplantation tolerance in mice,” Journal of Clinical Investigation, vol. 118, no. 11, pp. 3619–3628, 2008. View at Publisher · View at Google Scholar · View at Scopus
  173. F. Casiraghi, N. Perico, and G. Remuzzi, “Mesenchymal stromal cells to promote solid organ transplantation tolerance,” Current Opinion in Organ Transplantation, vol. 18, no. 1, pp. 51–58, 2013. View at Publisher · View at Google Scholar
  174. W. Ge, J. Jiang, M. L. Baroja et al., “Infusion of mesenchymal stem cells and rapamycin synergize to attenuate alloimmune responses and promote cardiac allograft tolerance,” American Journal of Transplantation, vol. 9, no. 8, pp. 1760–1772, 2009. View at Publisher · View at Google Scholar · View at Scopus
  175. R. Maccario, M. Podestà, A. Moretta et al., “Interaction of human mesenchymal stem cells with cells involved in alloantigen-specific immune response favors the differentiation of CD4+ T-cell subsets expressing a regulatory/suppressive phenotype,” Haematologica, vol. 90, no. 4, pp. 516–525, 2005. View at Google Scholar · View at Scopus
  176. D. Mougiakakos, R. Jitschin, C. C. Johansson, R. Okita, R. Kiessling, and K. Le Blanc, “The impact of inflammatory licensing on heme oxygenase-1-mediated induction of regulatory T cells by human mesenchymal stem cells,” Blood, vol. 117, no. 18, pp. 4826–4835, 2011. View at Publisher · View at Google Scholar · View at Scopus
  177. W. T. Hsu, C. H. Lin, B. L. Chiang, H. Y. Jui, K. K. Wu, and C. M. Lee, “Prostaglandin E2 potentiates mesenchymal stem cell-induced IL-10+IFN-γ+CD4+ regulatory T cells to control transplant arteriosclerosis,” The Journal of Immunology, vol. 190, no. 5, pp. 2372–2380, 2013. View at Publisher · View at Google Scholar