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Journal of Allergy
Volume 2012 (2012), Article ID 948901, 9 pages
http://dx.doi.org/10.1155/2012/948901
Review Article

Regulatory T Cells and the Control of the Allergic Response

1Instituto de Medicina Molecular, Cellular Immunology Unit, Faculdade de Medicina da Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisbon, Portugal
2Instituto Gulbenkian de Ciência, Cellular Immunology Unit, 2781-901 Oeiras, Portugal

Received 16 June 2012; Accepted 28 August 2012

Academic Editor: Maria Leite-de-Moraes

Copyright © 2012 Ana Agua-Doce and Luis Graca. 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. T. Takahashi, Y. Kuniyasu, M. Toda et al., “Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state,” International Immunology, vol. 10, no. 12, pp. 1969–1980, 1998. View at Scopus
  2. J. Douwes, C. Brooks, C. van Dalen, and N. Pearce, “Importance of allergy in asthma: an epidemiologic perspective,” Current Allergy and Asthma Reports, vol. 11, no. 5, pp. 434–444, 2011. View at Publisher · View at Google Scholar · View at Scopus
  3. A. Y. Rudensky, “Regulatory T cells and Foxp3,” Immunological Reviews, vol. 241, no. 1, pp. 260–268, 2011. View at Publisher · View at Google Scholar · View at Scopus
  4. S. Sakaguchi, K. Wing, and M. Miyara, “Regulatory T cells—a brief history and perspective,” European Journal of Immunology, vol. 37, supplement 1, pp. S116–S123, 2007. View at Publisher · View at Google Scholar · View at Scopus
  5. X. Valencia and P. E. Lipsky, “CD4+CD25+Foxp3+ regulatory T cells in autoimmune diseases,” Nature Clinical Practice Rheumatology, vol. 3, no. 11, pp. 619–626, 2007. View at Publisher · View at Google Scholar · View at Scopus
  6. E. M. Ling, T. Smith, X. D. Nguyen et al., “Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease,” The Lancet, vol. 363, no. 9409, pp. 608–615, 2004. View at Publisher · View at Google Scholar · View at Scopus
  7. H. Waldmann, T. C. Chen, L. Graca et al., “Regulatory T cells in transplantation,” Seminars in Immunology, vol. 18, no. 2, pp. 111–119, 2006. View at Publisher · View at Google Scholar · View at Scopus
  8. L. Graca, A. Le Moine, S. P. Cobbold, and H. Waldmann, “Dominant transplantation tolerance: opinion,” Current Opinion in Immunology, vol. 15, no. 5, pp. 499–506, 2003. View at Publisher · View at Google Scholar · View at Scopus
  9. 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 Publisher · View at Google Scholar · View at Scopus
  10. F. Cottrez, S. D. Hurst, R. L. Coffman, and H. Groux, “T regulatory cells 1 inhibit a Th2-specific response in vivo,” Journal of Immunology, vol. 165, no. 9, pp. 4848–4853, 2000. View at Scopus
  11. S. Navarro, G. Cossalter, C. Chiavaroli et al., “The oral administration of bacterial extracts prevents asthma via the recruitment of regulatory T cells to the airways,” Mucosal Immunology, vol. 4, no. 1, pp. 53–65, 2011. View at Publisher · View at Google Scholar · View at Scopus
  12. A. Suto, H. Nakajima, S. I. Kagami, K. Suzuki, Y. Saito, and I. Iwamoto, “Role of CD4+ CD25+ regulatory T cells in T helper 2 cell-mediated allergic inflammation in the airways,” American Journal of Respiratory and Critical Care Medicine, vol. 164, no. 4, pp. 680–687, 2001. View at Scopus
  13. C. L. Bennett, J. Christie, F. Ramsdell et al., “The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of Foxp3,” Nature Genetics, vol. 27, no. 1, pp. 20–21, 2001. View at Publisher · View at Google Scholar · View at Scopus
  14. M. A. Curotto de Lafaille and J. J. Lafaille, “Natural and adaptive Foxp3+ regulatory T cells: more of the same or a division of labor?” Immunity, vol. 30, no. 5, pp. 626–635, 2009. View at Publisher · View at Google Scholar · View at Scopus
  15. W. Chen, W. Jin, N. Hardegen et al., “Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3,” Journal of Experimental Medicine, vol. 198, no. 12, pp. 1875–1886, 2003. View at Publisher · View at Google Scholar · View at Scopus
  16. A. Agua-Doce and L. Graca, “Prevention of house dust mite induced allergic airways disease in mice through immune tolerance,” PLoS ONE, vol. 6, no. 7, Article ID e22320, 2011. View at Publisher · View at Google Scholar · View at Scopus
  17. D. H. Strickland, P. A. Stumbles, G. R. Zosky et al., “Reversal of airway hyperresponsiveness by induction of airway mucosal CD4+CD25+ regulatory T cells,” Journal of Experimental Medicine, vol. 203, no. 12, pp. 2649–2660, 2006. View at Publisher · View at Google Scholar · View at Scopus
  18. J. Kearley, J. E. Barker, D. S. Robinson, and C. M. Lloyd, “Resolution of airway inflammation and hyperreactivity after in vivo transfer of CD4+CD25+ regulatory T cells is interleukin 10 dependent,” Journal of Experimental Medicine, vol. 202, no. 11, pp. 1539–1547, 2005. View at Publisher · View at Google Scholar · View at Scopus
  19. I. P. Lewkowich, N. S. Herman, K. W. Schleifer et al., “CD4+CD25+ T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function,” Journal of Experimental Medicine, vol. 202, no. 11, pp. 1549–1561, 2005. View at Publisher · View at Google Scholar · View at Scopus
  20. W. Scherf, S. Burdach, and G. Hansen, “Reduced expression of transforming growth factor β1 exacerbates pathology in an experimental asthma model,” European Journal of Immunology, vol. 35, no. 1, pp. 198–206, 2005. View at Publisher · View at Google Scholar · View at Scopus
  21. A. Nakao, S. Miike, M. Hatano et al., “Blockade of transforming growth factor β/Smad signaling in T cells by overexpression of Smad7 enhances antigen-induced airway inflammation and airway reactivity,” Journal of Experimental Medicine, vol. 192, no. 2, pp. 151–158, 2000. View at Publisher · View at Google Scholar · View at Scopus
  22. G. Hansen, J. J. McIntire, V. P. Yeung et al., “CD4+ T helper cells engineered to produce latent TGF-β1 reverse allergen-induced airway hyperreactivity and inflammation,” Journal of Clinical Investigation, vol. 105, no. 1, pp. 61–70, 2000. View at Scopus
  23. A. Joetham, K. Takada, C. Taube et al., “Naturally occurring lung CD4+CD25+ T cell regulation of airway allergic responses depends on IL-10 induction of TGF- β1,” Journal of Immunology, vol. 178, no. 3, pp. 1433–1442, 2007. View at Scopus
  24. K. Kretschmer, I. Apostolou, D. Hawiger, K. Khazaie, M. C. Nussenzweig, and H. von Boehmer, “Inducing and expanding regulatory T cell populations by foreign antigen,” Nature Immunology, vol. 6, no. 12, pp. 1219–1227, 2005. View at Publisher · View at Google Scholar · View at Scopus
  25. M. Ostroukhova, C. Seguin-Devaux, T. B. Oriss et al., “Tolerance induced by inhaled antigen involves CD4+ T cells expressing membrane-bound TGF-β and FOXP3,” Journal of Clinical Investigation, vol. 114, no. 1, pp. 28–38, 2004. View at Publisher · View at Google Scholar · View at Scopus
  26. V. G. Oliveira, M. Caridade, R. S. Paiva, J. Demengeot, and L. Graca, “Sub-optimal CD4+ T-cell activation triggers autonomous TGF-β-dependent conversion to Foxp3+ regulatory T cells,” European Journal of Immunology, vol. 41, no. 5, pp. 1249–1255, 2011. View at Publisher · View at Google Scholar · View at Scopus
  27. L. Gorelik, P. E. Fields, and R. A. Flavell, “Cutting edge: TGF-β inhibits Th type 2 development through inhibition of GATA-3 expression,” Journal of Immunology, vol. 165, no. 9, pp. 4773–4777, 2000. View at Scopus
  28. V. L. Heath, E.E. Murphy, C. Crain, M.G. Tomlinson, and A. O'Garra, “TGF-β1 down-regulates Th2 development and results in decreased IL-4-induced STAT6 activation and GATA-3 expression,” European Journal of Immunology, vol. 30, no. 9, pp. 2639–2649, 2000. View at Publisher · View at Google Scholar
  29. C. H. Chen, C. Seguin-Devaux, N. A. Burke et al., “Transforming growth factor β blocks Tec kinase phosphorylation, Ca2+ influx, and NFATc translocation causing inhibition of T cell differentiation,” Journal of Experimental Medicine, vol. 197, no. 12, pp. 1689–1699, 2003. View at Publisher · View at Google Scholar · View at Scopus
  30. P. van Vlasselaer, J. Punnonen, and J. E. de Vries, “Transforming growth factor-β directs IgA switching in human B cells,” Journal of Immunology, vol. 148, no. 7, pp. 2062–2067, 1992. View at Scopus
  31. M. Gereke, S. Jung, J. Buer, and D. Bruder, “Alveolar type II epithelial cells present antigen to CD4+ T cells and induce Foxp3+ regulatory T cells,” American Journal of Respiratory and Critical Care Medicine, vol. 179, no. 5, pp. 344–355, 2009. View at Publisher · View at Google Scholar · View at Scopus
  32. D. Mucida, Y. Park, G. Kim et al., “Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid,” Science, vol. 317, no. 5835, pp. 256–260, 2007. View at Publisher · View at Google Scholar · View at Scopus
  33. S. Goswami, P. Angkasekwinai, M. Shan et al., “Divergent functions for airway epithelial matrix metalloproteinase 7 and retinoic acid in experimental asthma,” Nature Immunology, vol. 10, no. 5, pp. 496–503, 2009. View at Publisher · View at Google Scholar · View at Scopus
  34. H. Takaki, K. Ichiyama, K. Koga et al., “STAT6 inhibits TGF-β1-mediated Foxp3 induction through direct binding to the Foxp3 promoter, which is reverted by retinoic acid receptor,” The Journal of Biological Chemistry, vol. 283, no. 22, pp. 14955–14962, 2008. View at Publisher · View at Google Scholar · View at Scopus
  35. M. Veldhoen, C. Uyttenhove, J. van Snick et al., “Transforming growth factor-β “reprograms” the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset,” Nature Immunology, vol. 9, no. 12, pp. 1341–1346, 2008. View at Publisher · View at Google Scholar · View at Scopus
  36. T. Korn, M. Mitsdoerffer, A. L. Croxford et al., “IL-6 controls Th17 immunity in vivo by inhibiting the conversion of conventional T cells into Foxp3+ regulatory T cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 47, pp. 18460–18465, 2008. View at Publisher · View at Google Scholar · View at Scopus
  37. M. Veldhoen, R. J. Hocking, R. A. Flavell, and B. Stockinger, “Signals mediated by transforming growth factor-β initiate autoimmune encephalomyelitis, but chronic inflammation is needed to sustain disease,” Nature Immunology, vol. 7, no. 11, pp. 1151–1156, 2006. View at Publisher · View at Google Scholar · View at Scopus
  38. T. Makinde, R. F. Murphy, and D. K. Agrawal, “The regulatory role of TGF-β in airway remodeling in asthma,” Immunology and Cell Biology, vol. 85, no. 5, pp. 348–356, 2007. View at Publisher · View at Google Scholar · View at Scopus
  39. Y. P. Rubtsov, J. P. Rasmussen, E. Y. Chi et al., “Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces,” Immunity, vol. 28, no. 4, pp. 546–558, 2008. View at Publisher · View at Google Scholar · View at Scopus
  40. C. A. Akdis, T. Blesken, M. Akdis, B. Wüthrich, and K. Blaser, “Role of interleukin 10 in specific immunotherapy,” Journal of Clinical Investigation, vol. 102, no. 1, pp. 98–106, 1998. View at Scopus
  41. O. Akbari, G. J. Freeman, E. H. Meyer et al., “Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity,” Nature Medicine, vol. 8, no. 9, pp. 1024–1032, 2002. View at Publisher · View at Google Scholar · View at Scopus
  42. A. O'Garra, F. J. Barrat, A. G. Castro, A. Vicari, and C. Hawrylowicz, “Strategies for use of IL-10 or its antagonists in human disease,” Immunological Reviews, vol. 223, no. 1, pp. 114–131, 2008. View at Publisher · View at Google Scholar · View at Scopus
  43. T. Nabe, A. Ikedo, F. Hosokawa et al., “Regulatory role of antigen-induced interleukin-10, produced by CD4+ T cells, in airway neutrophilia in a murine model for asthma,” European Journal of Pharmacology, vol. 677, no. 1–3, pp. 154–162, 2012. View at Publisher · View at Google Scholar · View at Scopus
  44. C. M. Lloyd and C. M. Hawrylowicz, “Regulatory T cells in asthma,” Immunity, vol. 31, no. 3, pp. 438–449, 2009. View at Publisher · View at Google Scholar · View at Scopus
  45. M. K. Levings and M. G. Roncarolo, “T-regulatory 1 cells: a novel subset of CD4+ T cells with immunoregulatory properties,” Journal of Allergy and Clinical Immunology, vol. 106, no. 1, part 2, pp. S109–S112, 2000. View at Scopus
  46. M. Battaglia and M. G. Roncarolo, “Immune intervention with T regulatory cells: past lessons and future perspectives for type 1 diabetes,” Seminars in Immunology, vol. 23, no. 3, pp. 182–194, 2011. View at Publisher · View at Google Scholar · View at Scopus
  47. G. Grünig, D. B. Corry, M. W. Leach, B. W. P. Seymour, V. P. Kurup, and D. M. Rennick, “Interleukin-10 is natural suppressor of cytokine production and inflammation in a murine model of allergic bronchopulmonary aspergillosis,” Journal of Experimental Medicine, vol. 185, no. 6, pp. 1089–1099, 1997. View at Publisher · View at Google Scholar · View at Scopus
  48. C. Zuany-Amorim, S. Haile, D. Leduc et al., “Interleukin-10 inhibits antigen-induced cellular recruitment into the airways of sensitized mice,” Journal of Clinical Investigation, vol. 95, no. 6, pp. 2644–2651, 1995. View at Scopus
  49. L. Hummelshoj, L. P. Ryder, and L. K. Poulsen, “The role of the interleukin-10 subfamily members in immunoglobulin production by human B cells,” Scandinavian Journal of Immunology, vol. 64, no. 1, pp. 40–47, 2006. View at Publisher · View at Google Scholar · View at Scopus
  50. S. J. Till, J. N. Francis, K. Nouri-Aria, and S. R. Durham, “Mechanisms of immunotherapy,” Journal of Allergy and Clinical Immunology, vol. 113, no. 6, pp. 1025–1034, 2004. View at Publisher · View at Google Scholar · View at Scopus
  51. M. Akdis and C. A. Akdis, “Mechanisms of allergen-specific immunotherapy,” Journal of Allergy and Clinical Immunology, vol. 119, no. 4, pp. 780–789, 2007. View at Publisher · View at Google Scholar · View at Scopus
  52. F. Meiler, J. Zumkehr, S. Klunker, B. Rückert, C. A. Akdis, and M. Akdis, “In vivo switch to IL-10-secreting T regulatory cells in high dose allergen exposure,” Journal of Experimental Medicine, vol. 205, no. 12, pp. 2887–2898, 2008. View at Publisher · View at Google Scholar · View at Scopus
  53. A. M. Thornton, P. E. Korty, D. Q. Tran et al., “Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells,” Journal of Immunology, vol. 184, no. 7, pp. 3433–3441, 2010. View at Publisher · View at Google Scholar · View at Scopus
  54. D. Haribhai, W. Lin, B. Edwards et al., “A central role for induced regulatory T cells in tolerance induction in experimental colitis,” Journal of Immunology, vol. 182, no. 6, pp. 3461–3468, 2009. View at Publisher · View at Google Scholar · View at Scopus
  55. S. Floess, J. Freyer, C. Siewert et al., “Epigenetic control of the Foxp3 locus in regulatory T cells,” PLoS Biology, vol. 5, no. 2, article e38, 2007. View at Publisher · View at Google Scholar · View at Scopus
  56. J. K. Polansky, K. Kretschmer, J. Freyer et al., “DNA methylation controls Foxp3 gene expression,” European Journal of Immunology, vol. 38, no. 6, pp. 1654–1663, 2008. View at Publisher · View at Google Scholar · View at Scopus
  57. T. Miyao, S. Floess, R. Setoguchi et al., “Plasticity of Foxp3+ T cells reflects promiscuous Foxp3 expression in conventional T cells but not reprogramming of regulatory T cells,” Immunity, vol. 36, no. 2, pp. 262–275, 2012. View at Publisher · View at Google Scholar · View at Scopus
  58. Y. Zheng, S. Josefowicz, A. Chaudhry, X. P. Peng, K. Forbush, and A. Y. Rudensky, “Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate,” Nature, vol. 463, no. 7282, pp. 808–812, 2010. View at Publisher · View at Google Scholar · View at Scopus
  59. Y. Tone, K. Furuuchi, Y. Kojima, M. L. Tykocinski, M. I. Greene, and M. Tone, “Smad3 and NFAT cooperate to induce Foxp3 expression through its enhancer,” Nature Immunology, vol. 9, no. 2, pp. 194–202, 2008. View at Publisher · View at Google Scholar · View at Scopus
  60. Y. Liu, P. Zhang, J. Li, A. B. Kulkarni, S. Perruche, and W. Chen, “A critical function for TGF-β signaling in the development of natural CD4+CD25+Foxp3+ regulatory T cells,” Nature Immunology, vol. 9, no. 6, pp. 632–640, 2008. View at Publisher · View at Google Scholar · View at Scopus
  61. A. Kitoh, M. Ono, Y. Naoe et al., “Indispensable role of the Runx1-Cbfβ transcription complex for in vivo-suppressive function of Foxp3+ regulatory T cells,” Immunity, vol. 31, no. 4, pp. 609–620, 2009. View at Publisher · View at Google Scholar · View at Scopus
  62. Y. Wang, M. Su, and Y. Wan, “An essential role of the transcription factor GATA-3 for the function of regulatory T cells,” Immunity, vol. 35, no. 3, pp. 337–348, 2011. View at Publisher · View at Google Scholar · View at Scopus
  63. G. Hintzen, L. Ohl, M. L. Del Rio et al., “Induction of tolerance to innocuous inhaled antigen relies on a CCR7-dependent dendritic cell-mediated antigen transport to the bronchial lymph node,” Journal of Immunology, vol. 177, no. 10, pp. 7346–7354, 2006. View at Scopus
  64. O. Akbari, P. Stock, A. K. Singh et al., “PD-L1 and PD-L2 modulate airway inflammation and iNKT-cell-dependent airway hyperreactivity in opposing directions,” Mucosal Immunology, vol. 3, no. 1, pp. 81–91, 2010. View at Publisher · View at Google Scholar · View at Scopus
  65. T. V. Moore, B. S. Clay, J. L. Cannon, A. Histed, R. A. Shilling, and A. I. Sperling, “Inducible costimulator controls migration of T cells to the lungs via down-regulation of CCR7 and CD62L,” American Journal of Respiratory Cell and Molecular Biology, vol. 45, no. 4, pp. 843–850, 2011. View at Publisher · View at Google Scholar · View at Scopus
  66. B. D. Sather, P. Treuting, N. Perdue et al., “Altering the distribution of Foxp3+ regulatory T cells results in tissue-specific inflammatory disease,” Journal of Experimental Medicine, vol. 204, no. 6, pp. 1335–1347, 2007. View at Publisher · View at Google Scholar · View at Scopus
  67. T. Imai, M. Nagira, S. Takagi, et al., “Selective recruitment of CCR4-bearing Th2 cells toward antigen-presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine,” International Immunology, vol. 11, no. 1, pp. 81–88, 1999. View at Publisher · View at Google Scholar
  68. B. M. Hall, N. D. Verma, G. T. Tran, and S. J. Hodgkinson, “Distinct regulatory CD4 + T cell subsets; differences between naïve and antigen specific T regulatory cells,” Current Opinion in Immunology, vol. 23, no. 5, pp. 641–647, 2011. View at Publisher · View at Google Scholar · View at Scopus
  69. M. A. Linterman, W. Pierson, S. K. Lee et al., “Foxp3+ follicular regulatory T cells control the germinal center response,” Nature Medicine, vol. 17, no. 8, pp. 975–982, 2011. View at Publisher · View at Google Scholar · View at Scopus
  70. M. A. Koch, G. Tucker-Heard, N. R. Perdue, J. R. Killebrew, K. B. Urdahl, and D. J. Campbell, “The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation,” Nature Immunology, vol. 10, no. 6, pp. 595–602, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. E. Bettelli, Y. Carrier, W. Gao et al., “Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells,” Nature, vol. 441, no. 7090, pp. 235–238, 2006. View at Publisher · View at Google Scholar · View at Scopus
  72. L. Zhou, J. E. Lopes, M. M. W. Chong et al., “TGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORγt function,” Nature, vol. 453, no. 7192, pp. 236–240, 2008. View at Publisher · View at Google Scholar · View at Scopus
  73. N. M. Haynes, C. D. C. Allen, R. Lesley, K. M. Ansel, N. Killeen, and J. G. Cyster, “Role of CXCR5 and CCR7 in follicular Th cell positioning and appearance of a programmed cell death gene-1High germinal center-associated subpopulation,” Journal of Immunology, vol. 179, no. 8, pp. 5099–5108, 2007. View at Scopus
  74. D. Yu, S. Rao, L. M. Tsai et al., “The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment,” Immunity, vol. 31, no. 3, pp. 457–468, 2009. View at Publisher · View at Google Scholar · View at Scopus
  75. R. I. Nurieva, Y. Chung, G. J. Martinez et al., “Bcl6 mediates the development of T follicular helper cells,” Science, vol. 325, no. 5943, pp. 1001–1005, 2009. View at Publisher · View at Google Scholar · View at Scopus
  76. R. I. Nurieva, Y. Chung, D. Hwang et al., “Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages,” Immunity, vol. 29, no. 1, pp. 138–149, 2008. View at Publisher · View at Google Scholar · View at Scopus
  77. D. Breitfeld, L. Ohl, E. Kremmer et al., “Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production,” Journal of Experimental Medicine, vol. 192, no. 11, pp. 1545–1552, 2000. View at Publisher · View at Google Scholar · View at Scopus
  78. P. Schaerli, K. Willimann, A. B. Lang, M. Lipp, P. Loetscher, and B. Moser, “CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function,” Journal of Experimental Medicine, vol. 192, no. 11, pp. 1553–1562, 2000. View at Publisher · View at Google Scholar · View at Scopus
  79. I. Wollenberg, A. Agua-Doce, A. Hernández et al., “Regulation of the germinal center reaction by Foxp3+ follicular regulatory T cells,” Journal of Immunology, vol. 187, no. 9, pp. 4553–4560, 2011. View at Publisher · View at Google Scholar · View at Scopus
  80. Y. Chung, S. Tanaka, F. Chu et al., “Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions,” Nature Medicine, vol. 17, no. 8, pp. 983–988, 2011. View at Publisher · View at Google Scholar · View at Scopus
  81. H. W. Lim, P. Hillsamer, and C. H. Kim, “Regulatory T cells can migrate to follicles upon T cell activation and suppress GC-Th cells and GC-Th cell-driven B cell responses,” Journal of Clinical Investigation, vol. 114, no. 11, pp. 1640–1649, 2004. View at Publisher · View at Google Scholar · View at Scopus
  82. P. P. Chang, P. Barral, J. Fitch et al., “Identification of Bcl-6-dependent follicular helper NKT cells that provide cognate help for B cell responses,” Nature Immunology, vol. 13, no. 1, pp. 35–43, 2012. View at Publisher · View at Google Scholar · View at Scopus
  83. I. L. King, A. Fortier, M. Tighe et al., “Invariant natural killer T cells direct B cell responses to cognate lipid antigen in an IL-21-dependent manner,” Nature Immunology, vol. 13, no. 1, pp. 44–50, 2012. View at Publisher · View at Google Scholar · View at Scopus
  84. O. Akbari, P. Stock, E. Meyer et al., “Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity,” Nature Medicine, vol. 9, no. 5, pp. 582–588, 2003. View at Publisher · View at Google Scholar · View at Scopus
  85. M. Lisbonne, S. Diem, A. de Castro Keller et al., “Cutting edge: invariant Vα14 NKT cells are required for allergen-induced airway inflammation and hyperreactivity in an experimental asthma model,” Journal of Immunology, vol. 171, no. 4, pp. 1637–1641, 2003. View at Scopus
  86. M. L. Michel, A. C. Keller, C. Paget et al., “Identification of an IL-17-producing NK1.1neg iNKT cell population involved in airway neutrophilia,” Journal of Experimental Medicine, vol. 204, no. 5, pp. 995–1001, 2007. View at Publisher · View at Google Scholar · View at Scopus
  87. J. M. Coquet, S. Chakravarti, K. Kyparissoudis et al., “Diverse cytokine production by NKT cell subsets and identification of an IL-17-producing CD4-NK1.1- NKT cell population,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 32, pp. 11287–11292, 2008. View at Publisher · View at Google Scholar · View at Scopus
  88. M. Monteiro, C. F. Almeida, M. Caridade et al., “Identification of regulatory Foxp3+ invariant NKT cells induced by TGF-β,” Journal of Immunology, vol. 185, no. 4, pp. 2157–2163, 2010. View at Publisher · View at Google Scholar · View at Scopus
  89. L. T. Mars, L. Araujo, P. Kerschen et al., “Invariant NKT cells inhibit development of the Th17 lineage,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 15, pp. 6238–6243, 2009. View at Publisher · View at Google Scholar · View at Scopus
  90. L. Moreira-Teixeira, M. Resende, O. Devergne et al., “Rapamycin combined with TGF-β converts human invariant NKT Cells into suppressive Foxp3+ regulatory cells,” Journal of Immunology, vol. 188, no. 2, pp. 624–631, 2012. View at Publisher · View at Google Scholar · View at Scopus
  91. J. E. Konkel and W. Chen, “Balancing acts: the role of TGF-β in the mucosal immune system,” Trends in Molecular Medicine, vol. 17, no. 11, pp. 668–676, 2011. View at Publisher · View at Google Scholar · View at Scopus
  92. V. Verhasselt, V. Milcent, J. Cazareth et al., “Breast milk-mediated transfer of an antigen induces tolerance and protection from allergic asthma,” Nature Medicine, vol. 14, no. 2, pp. 170–175, 2008. View at Publisher · View at Google Scholar · View at Scopus
  93. K. Atarashi, T. Tanoue, T. Shima et al., “Induction of colonic regulatory T cells by indigenous Clostridium species,” Science, vol. 331, no. 6015, pp. 337–341, 2011. View at Publisher · View at Google Scholar · View at Scopus
  94. M. J. Benson, K. Pino-Lagos, M. Rosemblatt, and R. J. Noelle, “All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation,” Journal of Experimental Medicine, vol. 204, no. 8, pp. 1765–1774, 2007. View at Publisher · View at Google Scholar · View at Scopus
  95. J. L. Coombes, K. R. R. Siddiqui, C. V. Arancibia-Cárcamo et al., “A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-β -and retinoic acid-dependent mechanism,” Journal of Experimental Medicine, vol. 204, no. 8, pp. 1757–1764, 2007. View at Publisher · View at Google Scholar · View at Scopus
  96. D. Bruce, S. Yu, J. H. Ooi, and M. T. Cantorna, “Converging pathways lead to overproduction of IL-17 in the absence of vitamin D signaling,” International Immunology, vol. 23, no. 8, pp. 519–528, 2011. View at Publisher · View at Google Scholar · View at Scopus
  97. F. J. Barrat, D. J. Cua, A. Boonstra et al., “In vitro generation of interleukin 10-producing regulatory CD4+ T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1)- and Th2-inducing cytokines,” Journal of Experimental Medicine, vol. 195, no. 5, pp. 603–616, 2002. View at Publisher · View at Google Scholar · View at Scopus
  98. G. Penna, A. Roncari, S. Amuchastegui et al., “Expression of the inhibitory receptor ILT3 on dendritic cells is dispensable for induction of CD4+Foxp3+ regulatory T cells by 1,25-dihydroxyvitamin D3,” Blood, vol. 106, no. 10, pp. 3490–3497, 2005. View at Publisher · View at Google Scholar · View at Scopus
  99. Z. Urry, E. Xystrakis, D. F. Richards et al., “Ligation of TLR9 induced on human IL-10-secreting Tregs by 1α,25-dihydroxyvitamin D3 abrogates regulatory function,” Journal of Clinical Investigation, vol. 119, no. 2, pp. 387–398, 2009. View at Publisher · View at Google Scholar · View at Scopus
  100. B. D. Mahon, A. Wittke, V. Weaver, and M. T. Cantorna, “The targets of vitamin D depend on the differentiation and activation status of CD4 positive T cells,” Journal of Cellular Biochemistry, vol. 89, no. 5, pp. 922–932, 2003. View at Publisher · View at Google Scholar · View at Scopus
  101. G. Noh and J. H. Lee, “Oral tolerance induction for human food allergy,” Inflammation and Allergy—Drug Targets, vol. 11, no. 2, pp. 131–142, 2012. View at Scopus
  102. C. A. Akdis and M. Akdis, “Mechanisms of allergen-specific immunotherapy,” Journal of Allergy and Clinical Immunology, vol. 127, no. 1, pp. 18–27, 2011. View at Publisher · View at Google Scholar · View at Scopus
  103. H. Fujita, M.B. Soyka, M. Akdis, and C.A. Akdis, “Mechanisms of allergen-specific immunotherapy,” Clinical and Translational Allergy, vol. 2, no. 1, article 2, 2012.
  104. M. Akdis, K. Blaser, and C. A. Akdis, “T regulatory cells in allergy: novel concepts in the pathogenesis, prevention, and treatment of allergic diseases,” Journal of Allergy and Clinical Immunology, vol. 116, no. 5, pp. 961–969, 2005. View at Publisher · View at Google Scholar · View at Scopus
  105. O. Palomares, G. Yaman, A. K. Azkur, T. Akkoc, M. Akdis, and C. A. Akdis, “Role of Treg in immune regulation of allergic diseases,” European Journal of Immunology, vol. 40, no. 5, pp. 1232–1240, 2010. View at Publisher · View at Google Scholar · View at Scopus
  106. M. Jutel, M. Akdis, F. Budak et al., “IL-10 and TGF-β cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy,” European Journal of Immunology, vol. 33, no. 5, pp. 1205–1214, 2003. View at Publisher · View at Google Scholar · View at Scopus
  107. J. M. Carballido, N. Carballido-Perrig, M. K. Kagi et al., “T cell epitope specificity in human allergic and nonallergic subjects to bee venom phospholipase A2,” Journal of Immunology, vol. 150, no. 8 I, pp. 3582–3591, 1993. View at Scopus
  108. T. A. E. Platts-Mills, J. W. Vaughan, K. Blumenthal, J. A. Woodfolk, and R. B. Sporik, “Decreased prevalence of asthma among children with high exposure to cat allergen: relevance of the modified Th2 response,” Mediators of Inflammation, vol. 10, no. 6, pp. 288–291, 2001. View at Publisher · View at Google Scholar · View at Scopus
  109. J. M. Kim and A. Rudensky, “The role of the transcription factor Foxp3 in the development of regulatory T cells,” Immunological Reviews, vol. 212, pp. 86–98, 2006. View at Publisher · View at Google Scholar · View at Scopus
  110. L. Graca, T. C. Chen, A. L. Moine, S. P. Cobbold, D. Howie, and H. Waldmann, “Dominant tolerance: activation thresholds for peripheral generation of regulatory T cells,” Trends in Immunology, vol. 26, no. 3, pp. 130–135, 2005. View at Publisher · View at Google Scholar · View at Scopus
  111. C. Y. Lin, L. Graca, S. P. Cobbold, and H. Waldmann, “Dominant transplantation tolerance impairs CD8+ T cell function but not expansion,” Nature Immunology, vol. 3, no. 12, pp. 1208–1213, 2002. View at Publisher · View at Google Scholar · View at Scopus
  112. L. Graca, A. Le Moine, C. Y. Lin, P. J. Fairchild, S. P. Cobbold, and H. Waldmann, “Donor-specific transplantation tolerance: the paradoxical behavior of CD4+CD25+ T cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 27, pp. 10122–10126, 2004. View at Publisher · View at Google Scholar · View at Scopus
  113. S. Qin, S. P. Cobbold, H. Pope et al., “‘Infectious’ transplantation tolerance,” Science, vol. 259, no. 5097, pp. 974–977, 1993. View at Scopus
  114. J. Duarte, M. Caridade, and L. Graca, “CD4-blockade can induce protection from peanut-induced anaphylaxis,” Frontiers in Immunology, vol. 2, article 56, 2011. View at Publisher · View at Google Scholar
  115. B. Linhart, S. Bigenzahn, A. Hartl et al., “Costimulation blockade inhibits allergic sensitization but does not affect established allergy in a murine model of grass pollen allergy,” Journal of Immunology, vol. 178, no. 6, pp. 3924–3931, 2007. View at Scopus
  116. P. A. Taylor, T. M. Friedman, R. Korngold, R. J. Noelle, and B. R. Blazar, “Tolerance induction of alloreactive T cells via ex vivo blockade of the CD40:CD40L costimulatory pathway results in the generation of a potent immune regulatory cell,” Blood, vol. 99, no. 12, pp. 4601–4609, 2002. View at Publisher · View at Google Scholar · View at Scopus
  117. L. Graca, K. Honey, E. Adams, S. P. Cobbold, and H. Waldmann, “Cutting edge: anti-CD154 therapeutic antibodies induce infectious transplantation tolerance,” Journal of Immunology, vol. 165, no. 9, pp. 4783–4786, 2000. View at Scopus
  118. A. Tang, T. A. Judge, B. J. Nickoloff, and L. A. Turka, “Suppression of murine allergic contact dermatitis by CTLA4Ig: tolerance induction of Th2 responses requires additional blockade of CD40-ligand,” Journal of Immunology, vol. 157, no. 1, pp. 117–125, 1996. View at Scopus
  119. D. Seshasayee, W. P. Lee, M. Zhou et al., “In vivo blockade of OX40 ligand inhibits thymic stromal lymphopoietin driven atopic inflammation,” Journal of Clinical Investigation, vol. 117, no. 12, pp. 3868–3878, 2007. View at Publisher · View at Google Scholar · View at Scopus
  120. D. Green, “Factor VIII inhibitors: a 50-year perspective,” Haemophilia, vol. 17, no. 6, pp. 831–838, 2011. View at Publisher · View at Google Scholar · View at Scopus
  121. N. Emi Aikawa, J. F. de Carvalho, C. Artur Almeida Silva, and E. Bonfá, “Immunogenicity of anti-TNF-α agents in autoimmune diseases,” Clinical Reviews in Allergy and Immunology, vol. 38, no. 2-3, pp. 82–89, 2010. View at Publisher · View at Google Scholar · View at Scopus