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TheScientificWorldJOURNAL
Volume 11 (2011), Pages 2620-2634
http://dx.doi.org/10.1100/2011/768948
Review Article

Regulatory Immunotherapy in Bone Marrow Transplantation

Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA

Received 10 August 2011; Accepted 12 October 2011

Academic Editors: N. Miyahara, Y. Renaudineau, and J. Sidney

Copyright © 2011 Vanessa Morales-Tirado 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. D. W. Barnes, M. J. Corp, J. F. Loutit, and F. E. Neal, “Treatment of murine leukaemia with X rays and homologous bone marrow; preliminary communication,” The British Medical Journal, vol. 2, pp. 626–627, 1956. View at Google Scholar
  2. D. W. Barnes and J. F. Loutit, “Treatment of murine leukaemia with x-rays and homologous bone marrow. II,” The British Journal of Haematology, vol. 3, pp. 241–252, 1957. View at Google Scholar
  3. D. W. Barnes and J. F. Loutit, “‘Secondary disease‘ of radiation chimeras: a syndrome due to lymphoid aplasia,” Annals of the New York Academy of Sciences, vol. 99, pp. 374–385, 1962. View at Google Scholar
  4. E. D. Thomas, H. L. Lochte Jr., J. H. Cannon, O. D. Sahler, and J. W. Ferrebee, “Supralethal whole body irradiation and isologous marrow transplantation in man,” The Journal of Clinical Investigation, vol. 38, pp. 1709–1716, 1959. View at Google Scholar
  5. G. Mathe, J. L. Amiel, L. Schwarzenberg, A. Cattan, and M. Schneider, “Adoptive immunotherapy of acute leukemia: experimental and clinical results,” Cancer Research, vol. 25, no. 9, pp. 1525–1531, 1965. View at Google Scholar
  6. H. E. Kohrt, A. B. Pillai, R. Lowsky, and S. Strober, “NKT cells, Treg, and their interactions in bone marrow transplantation,” European Journal of Immunology, vol. 40, no. 7, pp. 1862–1869, 2010. View at Publisher · View at Google Scholar · View at PubMed
  7. C. A. Wysocki, A. Panoskaltsis-Mortari, B. R. Blazar, and J. S. Serody, “Leukocyte migration and graft-versus-host disease,” Blood, vol. 105, no. 11, pp. 4191–4199, 2005. View at Publisher · View at Google Scholar · View at PubMed
  8. R. E. Billingham, “The biology of graft-versus-host reactions,” Harvey Lectures, vol. 62, pp. 21–78, 1966. View at Google Scholar
  9. A. Bendelac, P. B. Savage, and L. Teyton, “The biology of NKT cells,” Annual Review of Immunology, vol. 25, pp. 297–336, 2007. View at Publisher · View at Google Scholar · View at PubMed
  10. L. Wu and L. Van Kaer, “Natural killer T cells in health and disease,” Frontiers in Bioscience, vol. 3, pp. 236–251, 2011. View at Google Scholar
  11. T. Kawano, J. Cui, Y. Koezuka et al., “CD1d-restricted and TCR-mediated activation of V(α)14 NKT cells by glycosylceramides,” Science, vol. 278, no. 5343, pp. 1626–1629, 1997. View at Publisher · View at Google Scholar
  12. D. Zeng, D. Lewis, S. Dejbakhsh-Jones et al., “Bone marrow NK1.1(-) and NK1.1(+) T cells reciprocally regulate acute graft versus host disease,” Journal of Experimental Medicine, vol. 189, no. 7, pp. 1073–1081, 1999. View at Publisher · View at Google Scholar
  13. O. Lantz and A. Bendelac, “An invariant T cell receptor α chain is used by a unique subset of major histocompatibility complex class I-specific CD4+ and CD4-8- T cells in mice and humans,” Journal of Experimental Medicine, vol. 180, no. 3, pp. 1097–1106, 1994. View at Publisher · View at Google Scholar
  14. M. Exley, J. Garcia, S. P. Balk, and S. Porcelli, “Requirements for CD1d recognition by human invariant Vα24+ CD4- CD8- T cells,” Journal of Experimental Medicine, vol. 186, no. 1, pp. 109–120, 1997. View at Publisher · View at Google Scholar
  15. M. A. Exley, R. Hou, A. Shaulov et al., “Selective activation, expansion, and monitoring of human iNKT cells with a monoclonal antibody specific for the TCR α-chain CDR3 loop,” European Journal of Immunology, vol. 38, no. 6, pp. 1756–1766, 2008. View at Publisher · View at Google Scholar · View at PubMed
  16. M. A. Exley, S. P. Balk, and S. B. Wilson, “Isolation and functional use of human NK T cells,” Current Protocols in Immunology, chapter 14, unit 14.11, 2003. View at Google Scholar
  17. F. Lan, D. Zeng, M. Higuchi, J. P. Higgins, and S. Strober, “Host conditioning with total lymphoid irradiation and antithymocyte globulin prevents graft-versus-host disease: the role of CD1-reactive natural killer T cells,” Biology of Blood and Marrow Transplantation, vol. 9, no. 6, pp. 355–363, 2003. View at Publisher · View at Google Scholar
  18. D. Hashimoto, S. Asakura, S. Miyake et al., “Stimulation of host NKT cells by synthetic glycolipid regulates acute graft-versus-host disease by inducing Th2 polarization of donor T cells,” Journal of Immunology, vol. 174, no. 1, pp. 551–556, 2005. View at Google Scholar
  19. A. B. Pillai, T. I. George, S. Dutt, P. Teo, and S. Strober, “Host NKT cells can prevent graft-versus-host disease and permit graft antitumor activity after bone marrow transplantation,” Journal of Immunology, vol. 178, no. 10, pp. 6242–6251, 2007. View at Google Scholar
  20. D. B. Leveson-Gower, J. A. Olson, E. I. Sega et al., “Low doses of natural killer T cells provide protection from acute graft-versus-host disease via an IL-4-dependent mechanism,” Blood, vol. 117, no. 11, pp. 3220–3229, 2011. View at Publisher · View at Google Scholar · View at PubMed
  21. A. B. Pillai, T. I. George, S. Dutt, and S. Strober, “Host natural killer T cells induce an interleukin-4-dependent expansion of donor CD4+CD25+Foxp3+ T regulatory cells that protects against graft-versus-host disease,” Blood, vol. 113, no. 18, pp. 4458–4467, 2009. View at Publisher · View at Google Scholar · View at PubMed
  22. R. Lowsky, T. Takahashi, P. L. Yin et al., “Protective conditioning for acute graft-versus-host disease,” The New England Journal of Medicine, vol. 353, no. 13, pp. 1321–1331, 2005. View at Publisher · View at Google Scholar · View at PubMed
  23. H. E. Kohrt, B. B. Turnbull, K. Heydari et al., “TLI and ATG conditioning with low risk of graft-versus-host disease retains antitumor reactions after allogeneic hematopoietic cell transplantation from related and unrelated donors,” Blood, vol. 114, no. 5, pp. 1099–1109, 2009. View at Publisher · View at Google Scholar · View at PubMed
  24. G. L. Cvetanovich and D. A. Hafler, “Human regulatory T cells in autoimmune diseases,” Current Opinion in Immunology, vol. 22, no. 6, pp. 753–760, 2010. View at Publisher · View at Google Scholar · View at PubMed
  25. S. Sakaguchi, N. Sakaguchi, M. Asano, M. Itoh, and M. Toda, “Immunologic self-tolerance maintained by activated T cells expressing IL- 2 receptor α-chains (CD25): breakdown of a single mechanism of self-tolerance causes various autoimmune diseases,” Journal of Immunology, vol. 155, no. 3, pp. 1151–1164, 1995. View at Google Scholar
  26. F. Powrie and D. Mason, “OX-22(high) CD4+ T cells induce wasting disease with multiple organ pathology: prevention by the OX-22(low) subset,” Journal of Experimental Medicine, vol. 172, no. 6, pp. 1701–1708, 1990. View at Publisher · View at Google Scholar
  27. F. Annunziato, P. Romagnani, L. Cosmi, E. Lazzeri, and S. Romagnani, “Chemokines and lymphopoiesis in human thymus,” Trends in Immunology, vol. 22, no. 5, pp. 277–281, 2001. View at Publisher · View at Google Scholar
  28. M. Papiernik, M. L. De Moraes, C. Pontoux, F. Vasseur, and C. Pénit, “Regulatory CD4 T cells: expression of IL-2Rα chain, resistance to clonal deletion and IL-2 dependency,” International Immunology, vol. 10, no. 4, pp. 371–378, 1998. View at Publisher · View at Google Scholar
  29. D. K. Sojka, Y. H. Huang, and D. J. Fowell, “Mechanisms of regulatory T-cell suppression—a diverse arsenal for a moving target,” Immunology, vol. 124, no. 1, pp. 13–22, 2008. View at Publisher · View at Google Scholar · View at PubMed
  30. S. Sakaguchi, “Naturally arising Foxp3-expressing CD25+ CD4+ regulatory T cells in immunological tolerance to self and non-self,” Nature Immunology, vol. 6, no. 4, pp. 345–352, 2005. View at Publisher · View at Google Scholar · View at PubMed
  31. E. M. Shevach, “Special regulatory T cell review: how I became a T suppressor/regulatory cell maven,” Immunology, vol. 123, no. 1, pp. 3–5, 2008. View at Publisher · View at Google Scholar · View at PubMed
  32. D. A. Vignali, L. W. Collison, and C. J. Workman, “How regulatory T cells work,” Nature Reviews Immunology, vol. 8, no. 7, pp. 523–532, 2008. View at Publisher · View at Google Scholar · View at PubMed
  33. J. D. Fontenot, M. A. Gavin, and A. Y. Rudensky, “Foxp3 programs the development and function of CD4+CD25+ regulatory T cells,” Nature Immunology, vol. 4, no. 4, pp. 330–336, 2003. View at Publisher · View at Google Scholar · View at PubMed
  34. S. Hori, T. Nomura, and S. Sakaguchi, “Control of regulatory T cell development by the transcription factor Foxp3,” Science, vol. 299, no. 5609, pp. 1057–1061, 2003. View at Publisher · View at Google Scholar · View at PubMed
  35. R. Khattri, T. Cox, S. A. Yasayko, and F. Ramsdell, “An essential role for Scurfin in CD4+CD25+ T regulatory cells,” Nature Immunology, vol. 4, no. 4, pp. 337–342, 2003. View at Publisher · View at Google Scholar · View at PubMed
  36. J. Shimizu, S. Yamazaki, T. Takahashi, Y. Ishida, and S. Sakaguchi, “Stimulation of CD25+CD4+ regulatory T cells through GITR breaks immunological self-tolerance,” Nature Immunology, vol. 3, no. 2, pp. 135–142, 2002. View at Publisher · View at Google Scholar · View at PubMed
  37. R. S. McHugh, M. J. Whitters, C. A. Piccirillo et al., “CD4+CD25+ Immunoregulatory T Cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor,” Immunity, vol. 16, no. 2, pp. 311–323, 2002. View at Publisher · View at Google Scholar
  38. D. Zelenika, E. Adams, S. Humm et al., “Regulatory T cells overexpress a subset of Th2 gene transcripts,” Journal of Immunology, vol. 168, no. 3, pp. 1069–1079, 2002. View at Google Scholar
  39. J. D. Fontenot, J. P. Rasmussen, L. M. Williams, J. L. Dooley, A. G. Farr, and A. Y. Rudensky, “Regulatory T cell lineage specification by the forkhead transcription factor Foxp3,” Immunity, vol. 22, no. 3, pp. 329–341, 2005. View at Publisher · View at Google Scholar · View at PubMed
  40. Y. Y. Wan and R. A. Flavell, “Identifying Foxp3-expressing suppressor T cells with a bicistronic reporter,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 14, pp. 5126–5131, 2005. View at Publisher · View at Google Scholar · View at PubMed
  41. W. Liu, A. L. Putnam, Z. Xu-yu et al., “CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells,” Journal of Experimental Medicine, vol. 203, no. 7, pp. 1701–1711, 2006. View at Publisher · View at Google Scholar · View at PubMed
  42. M. Miyara, Y. Yoshioka, A. Kitoh et al., “Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor,” Immunity, vol. 30, no. 6, pp. 899–911, 2009. View at Publisher · View at Google Scholar · View at PubMed
  43. D. Valmori, A. Merlo, N. E. Souleimanian, C. S. Hesdorffer, and M. Ayyoub, “A peripheral circulating compartment of natural naive CD4+ Tregs,” Journal of Clinical Investigation, vol. 115, no. 7, pp. 1953–1962, 2005. View at Publisher · View at Google Scholar · View at PubMed
  44. M. Vocanson, A. Rozieres, A. Hennino et al., “Inducible costimulator (ICOS) is a marker for highly suppressive antigen-specific T cells sharing features of TH17/TH1 and regulatory T cells,” Journal of Allergy and Clinical Immunology, vol. 126, no. 2, pp. 280–289, 2010. View at Publisher · View at Google Scholar · View at PubMed
  45. S. F. Ziegler, “FOXP3: of mice and men,” Annual Review of Immunology, vol. 24, pp. 209–226, 2006. View at Publisher · View at Google Scholar · View at PubMed
  46. P. Hoffmann, T. J. Boeld, R. Eder et al., “Loss of FOXP3 expression in natural human CD4+ CD25+ regulatory T cells upon repetitive in vitro stimulation,” European Journal of Immunology, vol. 39, no. 4, pp. 1088–1097, 2009. View at Publisher · View at Google Scholar · View at PubMed
  47. L. M. Ebert, S. T. Bee, J. Browning et al., “The regulatory T cell-associated transcription factor FoxP3 is expressed by tumor cells,” Cancer Research, vol. 68, no. 8, pp. 3001–3009, 2008. View at Publisher · View at Google Scholar · View at PubMed
  48. T. Aarts-Riemens, M. E. Emmelot, L. F. Verdonck, and T. Mutis, “Forced overexpression of either of the two common human Foxp3 isoforms can iduce regulatory T cells from CD4+CD25- cells,” European Journal of Immunology, vol. 38, no. 5, pp. 1381–1390, 2008. View at Publisher · View at Google Scholar · View at PubMed
  49. S. E. Allan, L. Passarini, R. Bacchetta et al., “The role of 2 FOXP3 isoforms in the generation of human CD4+ Tregs,” Journal of Clinical Investigation, vol. 115, no. 11, pp. 3276–3284, 2005. View at Publisher · View at Google Scholar · View at PubMed
  50. J. Du, C. Huang, B. Zhou, and S. F. Ziegler, “Isoform-specific inhibition of RORα-mediated transcriptional activation by human FOXP3,” Journal of Immunology, vol. 180, no. 7, pp. 4785–4792, 2008. View at Google Scholar
  51. C. W. Ashley and C. Baecher-Allan, “Cutting edge: responder T cells regulate human DR+ effector regulatory T cell activity via Granzyme B,” Journal of Immunology, vol. 183, no. 8, pp. 4843–4847, 2009. View at Publisher · View at Google Scholar · View at PubMed
  52. S. Onizuka, I. Tawara, J. Shimizu, S. Sakaguchi, T. Fujita, and E. Nakayama, “Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor α) monoclonal antibody,” Cancer Research, vol. 59, no. 13, pp. 3128–3133, 1999. View at Google Scholar
  53. J. Shimizu, S. Yamazaki, and S. Sakaguchi, “Induction of tumor immunity by removing CD25+CD4+ T cells: a common basis between tumor immunity and autoimmunity,” Journal of Immunology, vol. 163, no. 10, pp. 5211–5218, 1999. View at Google Scholar
  54. P. A. Taylor, R. J. Noelle, and B. R. Blazar, “CD4+CD25+ immune regulatory cells are required for induction of tolerance to alloantigen via costimulatory blockade,” Journal of Experimental Medicine, vol. 193, no. 11, pp. 1311–1317, 2001. View at Publisher · View at Google Scholar
  55. 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
  56. M. Edinger, P. Hoffmann, J. Ermann et al., “CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation,” Nature Medicine, vol. 9, no. 9, pp. 1144–1150, 2003. View at Publisher · View at Google Scholar · View at PubMed
  57. J. Ermann, P. Hoffmann, M. Edinger et al., “Only the CD62L+ subpopulation of CD4+CD25+ regulatory T cells protects from lethal acute GVHD,” Blood, vol. 105, no. 5, pp. 2220–2226, 2005. View at Publisher · View at Google Scholar · View at PubMed
  58. V. H. Nguyen, R. Zeiser, D. L. DaSilva et al., “In vivo dynamics of regulatory T-cell trafficking and survival predict effective strategies to control graft-versus-host disease following allogeneic transplantation,” Blood, vol. 109, no. 6, pp. 2649–2656, 2007. View at Publisher · View at Google Scholar · View at PubMed
  59. M. Di Ianni, F. Falzetti, A. Carotti et al., “Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation,” Blood, vol. 117, no. 14, pp. 3921–3928, 2011. View at Publisher · View at Google Scholar · View at PubMed
  60. J. L. Riley, C. H. June, and B. R. Blazar, “Human T regulatory cell therapy: take a billion or so and call me in the morning,” Immunity, vol. 30, no. 5, pp. 656–665, 2009. View at Publisher · View at Google Scholar · View at PubMed
  61. M. Battaglia, A. Stabilini, B. Migliavacca, J. Horejs-Hoeck, T. Kaupper, and M. G. Roncarolo, “Rapamycin promotes expansion of functional CD4+CD25 +FOXP3+ regulatory T cells of both healthy subjects and type 1 diabetic patients,” Journal of Immunology, vol. 177, no. 12, pp. 8338–8347, 2006. View at Google Scholar
  62. M. Battaglia, A. Stabilini, and M. G. Roncarolo, “Rapamycin selectively expands CD4+CD25+FoxP3 + regulatory T cells,” Blood, vol. 105, no. 12, pp. 4743–4748, 2005. View at Publisher · View at Google Scholar · View at PubMed
  63. L. Passerini, S. E. Allan, M. Battaglia et al., “STAT5-signaling cytokines regulate the expression of FOXP3 in CD4+CD25+ regulatory T cells and CD4+ CD25- effector T cells,” International Immunology, vol. 20, no. 3, pp. 421–431, 2008. View at Publisher · View at Google Scholar · View at PubMed
  64. V. Morales-Tirado, D. G. Wichlan, T. E. Leimig, S. E. Street, K. A. Kasow, and J. M. Riberdy, “1alpha,25-dihydroxyvitamin D3 (vitamin D3) catalyzes suppressive activity on human natural regulatory T cells, uniquely modulates cell cycle progression, and augments FOXP3,” Clinical Immunology, vol. 138, pp. 212–221, 2011. View at Google Scholar
  65. S. E. Allan, R. Broady, S. Gregori et al., “CD4+ T-regulatory cells: toward therapy for human diseases,” Immunological Reviews, vol. 223, no. 1, pp. 391–421, 2008. View at Publisher · View at Google Scholar · View at PubMed
  66. M. K. Levings and M. G. Roncarolo, “Phenotypic and functional differences between human CD4 +CD25+ and type 1 regulatory T cells,” Current Topics in Microbiology and Immunology, vol. 293, pp. 303–326, 2005. View at Google Scholar
  67. M. G. Roncarlo and S. Gregori, “Is FOXP3 a bona fide marker for human regulatory T cells?” European Journal of Immunology, vol. 38, no. 4, pp. 925–927, 2008. View at Publisher · View at Google Scholar · View at PubMed
  68. A. Pillai, C. Hartford, C. Wang et al., “Favorable preliminary results using TLI/ATG-based immunomodulatory conditioning for matched unrelated donor allogeneic hematopoietic stem cell transplantation in pediatric severe aplastic anemia,” Pediatric Transplantation, vol. 15, no. 6, pp. 628–634, 2011. View at Publisher · View at Google Scholar · View at PubMed