Regulatory T cells control Th2-dominant murine autoimmune gastritis

Journal of Immunology

Volumn 197, Issue 1, 2016, Pages 27-41

  Harakal, Jessica ^a   Rival, Claudia ^a   Qiao, Hui ^a   Tung, Kenneth S ^a  

^a UNIVERSITY OF VIRGINIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AUTOANTIBODY; CYTOKINE; GAMMA INTERFERON; HYDROGEN POTASSIUM ADENOSINE TRIPHOSPHATASE; ILT3 PROTEIN; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G1 ANTIBODY; INTERFERON REGULATORY FACTOR 4; INTERLEUKIN 17; INTERLEUKIN 4; INTRINSIC FACTOR; LYMPHOCYTE ANTIGEN; PROGRAMMED DEATH 1 LIGAND 2; TRANSCRIPTION FACTOR FOXP3; UNCLASSIFIED DRUG; IMMUNOGLOBULIN G;

ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBODY RESPONSE; ARTICLE; AUTOIMMUNE DISEASE; AUTOIMMUNE GASTRITIS; CELL INFILTRATION; CONTROLLED STUDY; CYTOKINE PRODUCTION; DENDRITIC CELL; DISEASE SEVERITY; EOSINOPHIL; GASTRITIS; MOUSE; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROMOTER REGION; REGULATORY T LYMPHOCYTE; T CELL DEPLETION; TH2 CELL; ANIMAL; BLOOD; C57BL MOUSE; CELL CULTURE; HUMAN; IMMUNOLOGY; IMMUNOMODULATION; METABOLISM; STOMACH MUCOSA; STOMACH PARIETAL CELL; TH1 CELL;

ANIMALS; AUTOIMMUNE DISEASES; CELLS, CULTURED; GASTRIC MUCOSA; GASTRITIS; HUMANS; IMMUNOGLOBULIN G; IMMUNOMODULATION; INTERLEUKIN-4; MICE; MICE, INBRED C57BL; PARIETAL CELLS, GASTRIC; T-LYMPHOCYTES, REGULATORY; TH1 CELLS; TH2 CELLS;

EID: 84975257266     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1502344     Document Type: Article

References (135)

1. Xing, Y., and K. A. Hogquist. 2012. T-cell tolerance: central and peripheral. Cold Spring Harb. Perspect. Biol. 4: a006957.
2. Sakaguchi, S. 2004. Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu. Rev. Immunol. 22: 531-562.
3. Hori, S., T. Nomura, and S. Sakaguchi. 2003. Control of regulatory T cell development by the transcription factor Foxp3. Science 299: 1057-1061.
4. Fontenot, J. D., M. A. Gavin, and A. Y. Rudensky. 2003. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol. 4: 330-336.
5. Wan, Y. Y., and R. A. Flavell. 2007. Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression. Nature 445: 766-770.
6. Brunkow, M. E., E. W. Jeffery, K. A. Hjerrild, B. Paeper, L. B. Clark, S. A. Yasayko, J. E. Wilkinson, D. Galas, S. F. Ziegler, and F. Ramsdell. 2001. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat. Genet. 27: 68-73.
7. Khattri, R., T. Cox, S.-A. Yasayko, and F. Ramsdell. 2003. An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat. Immunol. 4: 337-342.
8. Bennett, C. L., J. Christie, F. Ramsdell, M. E. Brunkow, P. J. Ferguson, L. Whitesell, T. E. Kelly, F. T. Saulsbury, P. F. Chance, and H. D. Ochs. 2001. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat. Genet. 27: 20-21.
9. Torgerson, T. R., and H. D. Ochs. 2007. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked: forkhead box protein 3 mutations and lack of regulatory T cells. J. Allergy Clin. Immunol. 120: 744-750, quiz 751-752.
10. Jeffries, G. H., D. W. Hoskins, and M. H. Sleisenger. 1962. Antibody to intrinsic factor in serum from patients with pernicious anemia. J. Clin. Invest. 41: 1106-1115.
11. Irvine, W. J., S. H. Davies, S. Teitelbaum, I. W. Delamore, and A. W. Williams. 1965. The clinical and pathological significance of gastric parietal cell antibody. Ann. N. Y. Acad. Sci. 124: 657-691.
12. Karlsson, F. A., P. Burman, L. Lööf, and S. Mardh. 1988. Major parietal cell antigen in autoimmune gastritis with pernicious anemia is the acid-producing H+,K+-adenosine triphosphatase of the stomach. J. Clin. Invest. 81: 475-479.
13. Goldkorn, I., P. A. Gleeson, and B. H. Toh. 1989. Gastric parietal cell antigens of 60-90, 92, and 100-120 kDa associated with autoimmune gastritis and pernicious anemia. Role of N-glycans in the structure and antigenicity of the 60-90-kDa component. J. Biol. Chem. 264: 18768-18774.
14. Toh, B. H., P. A. Gleeson, R. J. Simpson, R. L. Moritz, J. M. Callaghan, I. Goldkorn, C. M. Jones, T. M. Martinelli, F. T. Mu, D. C. Humphris, et al. 1990. The 60-to 90-kDa parietal cell autoantigen associated with autoimmune gastritis is a beta subunit of the gastric H+/K(+)-ATPase (proton pump). Proc. Natl. Acad. Sci. USA 87: 6418-6422.
15. Jones, C. M., B. H. Toh, J. M. Pettitt, T. M. Martinelli, D. C. Humphris, J. M. Callaghan, I. Goldkorn, F. T. Mu, and P. A. Gleeson. 1991. Monoclonal antibodies specific for the core protein of the beta-subunit of the gastric proton pump (H+/K+ ATPase). An autoantigen targetted in pernicious anaemia. Eur. J. Biochem. 197: 49-59.
16. Borch, K., H. Renvall, and G. Liedberg. 1985. Gastric endocrine cell hyperplasia and carcinoid tumors in pernicious anemia. Gastroenterology 88: 638-648.
17. Armbrecht, U., R. W. Stockbrugger, J. Rode, G. G. Menon, and P. B. Cotton. 1990. Development of gastric dysplasia in pernicious anaemia: A clinical and endoscopic follow up study of 80 patients. Gut 31: 1105-1109.
18. Kokkola, A., S. M. Sjöblom, R. Haapiainen, P. Sipponen, P. Puolakkainen, and H. Järvinen. 1998. The risk of gastric carcinoma and carcinoid tumours in patients with pernicious anaemia. A prospective follow-up study. Scand. J. Gastroenterol. 33: 88-92.
19. Carmel, R. 1996. Prevalence of undiagnosed pernicious anemia in the elderly. Arch. Intern. Med. 156: 1097-1100.
20. Toh, B. H., I. R. van Driel, and P. A. Gleeson. 1997. Pernicious anemia. N. Engl. J. Med. 337: 1441-1448.
21. van Driel, I. R., E. Tu, and P. A. Gleeson. 2014. The Autoimmune Diseases. In The Autoimmune Diseases, 5th Ed., N. R. Rose, and I. R. Machay, eds. Academic Press, Cambridge, MA, p. 619-631.
22. Kojima, A., and R. T. Prehn. 1981. Genetic susceptibility to post-thymectomy autoimmune diseases in mice. Immunogenetics 14: 15-27.
23. Sakaguchi, S., K. Fukuma, K. Kuribayashi, and T. Masuda. 1985. Organspecific autoimmune diseases induced in mice by elimination of T cell subset. I. Evidence for the active participation of T cells in natural self-tolerance; deficit of a T cell subset as a possible cause of autoimmune disease. J. Exp. Med. 161: 72-87.
24. Fukuma, K., S. Sakaguchi, K. Kuribayashi, W. L. Chen, R. Morishita, K. Sekita, H. Uchino, and T. Masuda. 1988. Immunologic and clinical studies on murine experimental autoimmune gastritis induced by neonatal thymectomy. Gastroenterology 94: 274-283.
25. Tung, K. S. 1994. Mechanism of self-tolerance and events leading to autoimmune disease and autoantibody response. Clin. Immunol. Immunopathol. 73: 275-282.
26. Asano, M., M. Toda, N. Sakaguchi, and S. Sakaguchi. 1996. Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation. J. Exp. Med. 184: 387-396.
27. Sakaguchi, S., N. Sakaguchi, M. Asano, M. Itoh, and M. Toda. 1995. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 155: 1151-1164.
28. Sakaguchi, S., M. Toda, M. Asano, M. Itoh, S. S. Morse, and N. Sakaguchi. 1996. T cell-mediated maintenance of natural self-tolerance: its breakdown as a possible cause of various autoimmune diseases. J. Autoimmun. 9: 211-220.
29. Itoh, M., T. Takahashi, N. Sakaguchi, Y. Kuniyasu, J. Shimizu, F. Otsuka, and S. Sakaguchi. 1999. Thymus and autoimmunity: production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance. J. Immunol. 162: 5317-5326.
30. Tung, K. S., S. Smith, C. Teuscher, C. Cook, and R. E. Anderson. 1987. Murine autoimmune oophoritis, epididymoorchitis, and gastritis induced by day 3 thymectomy. Immunopathology. Am. J. Pathol. 126: 293-302.
31. DiPaolo, R. J., D. D. Glass, K. E. Bijwaard, and E. M. Shevach. 2005. CD4 +CD25+ T cells prevent the development of organ-specific autoimmune disease by inhibiting the differentiation of autoreactive effector T cells. J. Immunol. 175: 7135-7142.
32. Suri-Payer, E., A. Z. Amar, R. McHugh, K. Natarajan, D. H. Margulies, and E. M. Shevach. 1999. Post-thymectomy autoimmune gastritis: fine specificity and pathogenicity of anti-H/K ATPase-reactive T cells. Eur. J. Immunol. 29: 669-677.
33. Dujardin, H. C., O. Burlen-Defranoux, L. Boucontet, P. Vieira, A. Cumano, and A. Bandeira. 2004. Regulatory potential and control of Foxp3 expression in newborn CD4+ T cells. Proc. Natl. Acad. Sci. USA 101: 14473-14478.
34. Samy, E. T., K. M. Wheeler, R. J. Roper, C. Teuscher, and K. S. K. Tung. 2008. Cutting edge: Autoimmune disease in day 3 thymectomized mice is actively controlled by endogenous disease-specific regulatory T cells. J. Immunol. 180: 4366-4370.
35. Wheeler, K. M., E. T. Samy, and K. S. K. Tung. 2009. Cutting edge: normal regional lymph node enrichment of antigen-specific regulatory T cells with autoimmune disease-suppressive capacity. J. Immunol. 183: 7635-7638.
36. Gleeson, P. A., B. H. Toh, and I. R. van Driel. 1996. Organ-specific autoimmunity induced by lymphopenia. Immunol. Rev. 149: 97-125.
37. Monteiro, J. P., J. Farache, A. C. Mercadante, J. A. Mignaco, M. Bonamino, and A. Bonomo. 2008. Pathogenic effector T cell enrichment overcomes regulatory T cell control and generates autoimmune gastritis. J. Immunol. 181: 5895-5903.
38. Datta, S., and N. Sarvetnick. 2009. Lymphocyte proliferation in immunemediated diseases. Trends Immunol. 30: 430-438.
39. Kim, J. M., J. P. Rasmussen, and A. Y. Rudensky. 2007. Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat. Immunol. 8: 191-197.
40. Nyström, S. N., D. Bourges, S. Garry, E. M. Ross, I. R. van Driel, and P. A. Gleeson. 2014. Transient Treg-cell depletion in adult mice results in persistent self-reactive CD4(+) T-cell responses. Eur. J. Immunol. 44: 3621-3631.
41. Teh, C. E., and D. H. D. Gray. 2014. Can you rely on Treg cells on the rebound? Eur. J. Immunol. 44: 3504-3507.
42. Lahl, K., C. Loddenkemper, C. Drouin, J. Freyer, J. Arnason, G. Eberl, A. Hamann, H.Wagner, J. Huehn, and T. Sparwasser. 2007. Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease. J. Exp. Med. 204: 57-63.
43. Mayer, C. T., P. Ghorbani, A. A. Kuhl, P. Stuve, M. Hegemann, L. Berod, M. E. Gershwin, and T. Sparwasser. 2014. Few Foxp3+ regulatory T cells are sufficient to protect adult mice from lethal autoimmunity. Eur. J. Immunol. 44: 2990-3002.
44. Berod, L., P. Stuve, F. Varela, J. Behrends, M. Swallow, F. Kruse, F. Krull, P. Ghorbani, C. T. Mayer, C. Hölscher, and T. Sparwasser. 2014. Rapid rebound of the Treg compartment in DEREG mice limits the impact of Treg depletion on mycobacterial burden, but prevents autoimmunity. PLoS One 9: e102804.
45. Setiady, Y. Y., P. Pramoonjago, and K. S. K. Tung. 2004. Requirements of NK cells and proinflammatory cytokines in T cell-dependent neonatal autoimmune ovarian disease triggered by immune complex. J. Immunol. 173: 1051-1058.
46. Rival, C., E. Samy, Y. Setiady, and K. Tung. 2013. Cutting edge: Ly49C/I- neonatal NK cells predispose newborns to autoimmune ovarian disease induced by maternal autoantibody. J. Immunol. 191: 2865-2869.
47. Russell, S. E., A. M. Stefanska, M. Kubica, R. M. Horan, A. Mantovani, C. Garlanda, P. G. Fallon, and P. T. Walsh. 2013. Toll IL-1R8/single Ig IL-1-related receptor regulates psoriasiform inflammation through direct inhibition of innate IL-17A expression by gd T cells. J. Immunol. 191: 3337-3346.
48. Hill, D. A., C. Hoffmann, M. C. Abt, Y. Du, D. Kobuley, T. J. Kirn, F. D. Bushman, and D. Artis. 2010. Metagenomic analyses reveal antibioticinduced temporal and spatial changes in intestinal microbiota with associated alterations in immune cell homeostasis. Mucosal Immunol. 3: 148-158.
49. Alderuccio, F., B. H. Toh, P. A. Gleeson, and I. R. van Driel. 1995. A novel method for isolating mononuclear cells from the stomachs of mice with experimental autoimmune gastritis. Autoimmunity 21: 215-221.
50. Collison, L. W., and D. A. A. Vignali. 2011. In vitro Treg suppression assays. Methods Mol. Biol. 707: 21-37.
51. McHugh, R. S., and E. M. Shevach. 2002. Cutting edge: depletion of CD4+CD25+ regulatory T cells is necessary, but not sufficient, for induction of organ-specific autoimmune disease. J. Immunol. 168: 5979-5983.
52. Wheeler, K., S. Tardif, C. Rival, B. Luu, E. Bui, R. Del Rio, C. Teuscher, T. Sparwasser, D. Hardy, and K. S. K. Tung. 2011. Regulatory T cells control tolerogenic versus autoimmune response to sperm in vasectomy. Proc. Natl. Acad. Sci. USA 108: 7511-7516.
53. Zhang, X., S. Ing, A. Fraser, M. Chen, O. Khan, J. Zakem, W. Davis, and R. Quinet. 2013. Follicular helper T cells: new insights into mechanisms of autoimmune diseases. Ochsner J. 13: 131-139.
54. Lorenz, R. G., and J. I. Gordon. 1993. Use of transgenic mice to study regulation of gene expression in the parietal cell lineage of gastric units. J. Biol. Chem. 268: 26559-26570.
55. Ungar, B., S. Whittingham, and C. M. Francis. 1967. Pernicious anaemia: incidence and significance of circulating antibodies to intrinsic factor and to parietal cells. Australas. Ann. Med. 16: 226-229.
56. Carmel, R. 1992. Reassessment of the relative prevalences of antibodies to gastric parietal cell and to intrinsic factor in patients with pernicious anaemia: influence of patient age and race. Clin. Exp. Immunol. 89: 74-77.
57. Davidson, R. J., H. I. Atrah, and H. F. Sewell. 1989. Longitudinal study of circulating gastric antibodies in pernicious anaemia. J. Clin. Pathol. 42: 1092-1095.
58. Greenwood, D. L. V., and J. W. Sentry. 2007. Murine experimental autoimmune gastritis models refractive to development of intrinsic factor autoantibodies, cobalamin deficiency and pernicious anemia. Clin. Immunol. 122: 41-52.
59. Waterhouse, P., J. M. Penninger, E. Timms, A. Wakeham, A. Shahinian, K. P. Lee, C. B. Thompson, H. Griesser, and T. W. Mak. 1995. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science 270: 985-988.
60. Tivol, E. A., F. Borriello, A. N. Schweitzer, W. P. Lynch, J. A. Bluestone, and A. H. Sharpe. 1995. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 3: 541-547.
61. Bour-Jordan, H., J. L. Grogan, Q. Tang, J. A. Auger, R. M. Locksley, and J. A. Bluestone. 2003. CTLA-4 regulates the requirement for cytokine-induced signals in T(H)2 lineage commitment. Nat. Immunol. 4: 182-188.
62. Wing, K., Y. Onishi, P. Prieto-Martin, T. Yamaguchi, M. Miyara, Z. Fehervari, T. Nomura, and S. Sakaguchi. 2008. CTLA-4 control over Foxp3+ regulatory T cell function. Science 322: 271-275.
63. Walker, L. S. K. 2013. Treg and CTLA-4: two intertwining pathways to immune tolerance. J. Autoimmun. 45: 49-57.
64. Tian, L., J. A. Altin, L. E. Makaroff, D. Franckaert, M. C. Cook, C. C. Goodnow, J. Dooley, and A. Liston. 2011. Foxp3+ regulatory T cells exert asymmetric control over murine helper responses by inducing Th2 cell apoptosis. Blood 118: 1845-1853.
65. Ono, M., J. Shimizu, Y. Miyachi, and S. Sakaguchi. 2006. Control of autoimmune myocarditis and multiorgan inflammation by glucocorticoid-induced TNF receptor family-related protein(high), Foxp3-expressing CD25+ and CD25-regulatory T cells. J. Immunol. 176: 4748-4756.
66. Fontenot, J. D., J. P. Rasmussen, M. A. Gavin, and A. Y. Rudensky. 2005. A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nat. Immunol. 6: 1142-1151.
67. Komatsu, N., M. E. Mariotti-Ferrandiz, Y. Wang, B. Malissen, H. Waldmann, and S. Hori. 2009. Heterogeneity of natural Foxp3+ T cells: A committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity. Proc. Natl. Acad. Sci. USA 106: 1903-1908.
68. Komatsu, N., K. Okamoto, S. Sawa, T. Nakashima, M. Oh-hora, T. Kodama, S. Tanaka, J. A. Bluestone, and H. Takayanagi. 2014. Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis. Nat. Med. 20: 62-68.
69. Zheng, Y., A. Chaudhry, A. Kas, P. deRoos, J. M. Kim, T.-T. Chu, L. Corcoran, P. Treuting, U. Klein, and A. Y. Rudensky. 2009. Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control T(H)2 responses. Nature 458: 351-356.
70. Levine, A. G., A. Arvey, W. Jin, and A. Y. Rudensky. 2014. Continuous requirement for the TCR in regulatory T cell function. Nat. Immunol. 15: 1070-1078.
71. Finkelman, F. D., I. M. Katona, T. R. Mosmann, and R. L. Coffman. 1988. IFNgamma regulates the isotypes of Ig secreted during in vivo humoral immune responses. J. Immunol. 140: 1022-1027.
72. Finkelman, F. D., I. M. Katona, J. F. Urban, Jr., J. Holmes, J. Ohara, A. S. Tung, J. V. Sample, and W. E. Paul. 1988. IL-4 is required to generate and sustain in vivo IgE responses. J. Immunol. 141: 2335-2341.
73. Finkelman, F. D., J. Holmes, I. M. Katona, J. F. Urban, Jr., M. P. Beckmann, L. S. Park, K. A. Schooley, R. L. Coffman, T. R. Mosmann, and W. E. Paul. 1990. Lymphokine control of in vivo immunoglobulin isotype selection. Annu. Rev. Immunol. 8: 303-333.
74. Swain, S. L., A. D.Weinberg, M. English, and G. Huston. 1990. IL-4 directs the development of Th2-like helper effectors. J. Immunol. 145: 3796-3806.
75. Grunig, G., M. Warnock, A. E. Wakil, R. Venkayya, F. Brombacher, D. M. Rennick, D. Sheppard, M. Mohrs, D. D. Donaldson, R. M. Locksley, and D. B. Corry. 1998. Requirement for IL-13 independently of IL-4 in experimental asthma. Science 282: 2261-2263.
76. Curran, D. R., and L. Cohn. 2010. Advances in mucous cell metaplasia: A plug for mucus as a therapeutic focus in chronic airway disease. Am. J. Respir. Cell Mol. Biol. 42: 268-275.
77. Cohn, L., R. J. Homer, H. MacLeod, M. Mohrs, F. Brombacher, and K. Bottomly. 1999. Th2-induced airway mucus production is dependent on IL-4Ralpha, but not on eosinophils. J. Immunol. 162: 6178-6183.
78. Possa, S. S., E. A. Leick, C. M. Prado, M. A. Martins, and I. F. L. C. Tibério. 2013. Eosinophilic inflammation in allergic asthma. Front. Pharmacol. 4: 46.
79. Davoine, F., and P. Lacy. 2014. Eosinophil cytokines, chemokines, and growth factors: emerging roles in immunity. Front. Immunol. 5: 570.
80. Lee, J. J., D. Dimina, M. P. Macias, S. I. Ochkur, M. P. McGarry, K. R. O'Neill, C. Protheroe, R. Pero, T. Nguyen, S. A. Cormier, et al. 2004. Defining a link with asthma in mice congenitally deficient in eosinophils. Science 305: 1773-1776.
81. Riiser, A. 2015. The human microbiome, asthma, and allergy. Allergy Asthma Clin. Immunol. 11: 35.
82. Wu, W., H.-P. Liu, F. Chen, H. Liu, A. T. Cao, S. Yao, M. Sun, H. L. Evans-Marin, Y. Zhao, Q. Zhao, et al. 2016. Commensal A4 bacteria inhibit intestinal Th2-cell responses through induction of dendritic cell TGF-b production. Eur. J. Immunol. doi: 10.1002/eji.201546160.
83. Josefowicz, S. Z., R. E. Niec, H. Y. Kim, P. Treuting, T. Chinen, Y. Zheng, D. T. Umetsu, and A. Y. Rudensky. 2012. Extrathymically generated regulatory T cells control mucosal TH2 inflammation. Nature 482: 395-399.
84. Gao, Y., S. A. Nish, R. Jiang, L. Hou, P. Licona-Limón, J. S. Weinstein, H. Zhao, and R. Medzhitov. 2013. Control of T helper 2 responses by transcription factor IRF4-dependent dendritic cells. Immunity 39: 722-732.
85. Williams, J. W., M. Y. Tjota, B. S. Clay, B. Vander Lugt, H. S. Bandukwala, C. L. Hrusch, D. C. Decker, K. M. Blaine, B. R. Fixsen, H. Singh, et al. 2013. Transcription factor IRF4 drives dendritic cells to promote Th2 differentiation. Nat. Commun. 4: 2990.
86. Ulges, A., M. Klein, S. Reuter, B. Gerlitzki, M. Hoffmann, N. Grebe, V. Staudt, N. Stergiou, T. Bohn, T.-J. Bruhl, et al. 2015. Protein kinase CK2 enables regulatory T cells to suppress excessive TH2 responses in vivo. Nat. Immunol. 16: 267-275.
87. Agersborg, S. S., K. M. Garza, and K. S. Tung. 2001. Intestinal parasitism terminates self tolerance and enhances neonatal induction of autoimmune disease and memory. Eur. J. Immunol. 31: 851-859.
88. Pochanke, V., S. Hatak, H. Hengartner, R. M. Zinkernagel, and K. D. McCoy. 2006. Induction of IgE and allergic-type responses in fur mite-infested mice. Eur. J. Immunol. 36: 2434-2445.
89. Scarff, K. J., J. M. Pettitt, I. R. Van Driel, P. A. Gleeson, and B. H. Toh. 1997. Immunization with gastric H+/K(+)-ATPase induces a reversible autoimmune gastritis. Immunology 92: 91-98.
90. Barrett, S. P., P. A. Gleeson, H. de Silva, B. H. Toh, and I. R. van Driel. 1996. Interferon-gamma is required during the initiation of an organ-specific autoimmune disease. Eur. J. Immunol. 26: 1652-1655.
91. Stummvoll, G. H., R. J. DiPaolo, E. N. Huter, T. S. Davidson, D. Glass, J. M. Ward, and E. M. Shevach. 2008. Th1, Th2, and Th17 effector T cellinduced autoimmune gastritis differs in pathological pattern and in susceptibility to suppression by regulatory T cells. J. Immunol. 181: 1908-1916.
92. Tu, E., D. K. Y. Ang, S. A. Bellingham, T. V. Hogan, M. W. L. Teng, M. J. Smyth, A. F. Hill, and I. R. van Driel. 2012. Both IFN-g and IL-17 are required for the development of severe autoimmune gastritis. Eur. J. Immunol. 42: 2574-2583.
93. Racke, M. K., A. Bonomo, D. E. Scott, B. Cannella, A. Levine, C. S. Raine, E. M. Shevach, and M. Röcken. 1994. Cytokine-induced immune deviation as a therapy for inflammatory autoimmune disease. J. Exp. Med. 180: 1961-1966.
94. Elias, D., A. Meilin, V. Ablamunits, O. S. Birk, P. Carmi, S. Könen-Waisman, and I. R. Cohen. 1997. Hsp60 peptide therapy of NOD mouse diabetes induces a Th2 cytokine burst and downregulates autoimmunity to various beta-cell antigens. Diabetes 46: 758-764.
95. Tisch, R., B. Wang, and D. V. Serreze. 1999. Induction of glutamic acid decarboxylase 65-specific Th2 cells and suppression of autoimmune diabetes at late stages of disease is epitope dependent. J. Immunol. 163: 1178-1187.
96. Raphael, I., S. Nalawade, T. N. Eagar, and T. G. Forsthuber. 2015. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine 74: 5-17.
97. McHugh, R. S., E. M. Shevach, D. H. Margulies, and K. Natarajan. 2001. A T cell receptor transgenic model of severe, spontaneous organ-specific autoimmunity. Eur. J. Immunol. 31: 2094-2103.
98. Candon, S., R. S. McHugh, G. Foucras, K. Natarajan, E. M. Shevach, and D. H. Margulies. 2004. Spontaneous organ-specific Th2-mediated autoimmunity in TCR transgenic mice. J. Immunol. 172: 2917-2924.
99. Lafaille, J. J., F. V. Keere, A. L. Hsu, J. L. Baron, W. Haas, C. S. Raine, and S. Tonegawa. 1997. Myelin basic protein-specific T helper 2 (Th2) cells cause experimental autoimmune encephalomyelitis in immunodeficient hosts rather than protect them from the disease. J. Exp. Med. 186: 307-312.
100. Pakala, S. V., M. O. Kurrer, and J. D. Katz. 1997. T helper 2 (Th2) T cells induce acute pancreatitis and diabetes in immune-compromised nonobese diabetic (NOD) mice. J. Exp. Med. 186: 299-306.
101. Lou, Y. H., K. K. Park, S. Agersborg, P. Alard, and K. S. Tung. 2000. Retargeting T cell-mediated inflammation: A new perspective on autoantibody action. J. Immunol. 164: 5251-5257.
102. Poulin, M., and K. Haskins. 2000. Induction of diabetes in nonobese diabetic mice by Th2 T cell clones from a TCR transgenic mouse. J. Immunol. 164: 3072-3078.
103. Bettington, M., and I. Brown. 2013. Autoimmune gastritis: novel clues to histological diagnosis. Pathology 45: 145-149.
104. Bedeir, A. S., R. H. Lash, J. G. Lash, and M. B. Ray. 2010. Significant increase in IgG4+ plasma cells in gastric biopsy specimens from patients with pernicious anaemia. J. Clin. Pathol. 63: 999-1001.
105. Lundgren, M., U. Persson, P. Larsson, C. Magnusson, C. I. Smith, L. Hammarström, and E. Severinson. 1989. Interleukin 4 induces synthesis of IgE and IgG4 in human B cells. Eur. J. Immunol. 19: 1311-1315.
106. Gascan, H., J. F. Gauchat, M. G. Roncarolo, H. Yssel, H. Spits, and J. E. de Vries. 1991. Human B cell clones can be induced to proliferate and to switch to IgE and IgG4 synthesis by interleukin 4 and a signal provided by activated CD4+ T cell clones. J. Exp. Med. 173: 747-750.
107. Punnonen, J., G. Aversa, B. G. Cocks, A. N. McKenzie, S. Menon, G. Zurawski, R. de Waal Malefyt, and J. E. de Vries. 1993. Interleukin 13 induces interleukin 4-independent IgG4 and IgE synthesis and CD23 expression by human B cells. Proc. Natl. Acad. Sci. USA 90: 3730-3734.
108. Lahner, E., and B. Annibale. 2009. Pernicious anemia: new insights from a gastroenterological point of view. World J. Gastroenterol. 15: 5121-5128.
109. Fulkerson, P. C., and M. E. Rothenberg. 2013. Targeting eosinophils in allergy, inflammation and beyond. Nat. Rev. Drug Discov. 12: 117-129.
110. Jacobsen, E. A., S. I. Ochkur, R. S. Pero, A. G. Taranova, C. A. Protheroe, D. C. Colbert, N. A. Lee, and J. J. Lee. 2008. Allergic pulmonary inflammation in mice is dependent on eosinophil-induced recruitment of effector T cells. J. Exp. Med. 205: 699-710.
111. Chu, D. K., R. Jimenez-Saiz, C. P. Verschoor, T. D. Walker, S. Goncharova, A. Llop-Guevara, P. Shen, M. E. Gordon, N. G. Barra, J. D. Bassett, et al. 2014. Indigenous enteric eosinophils control DCs to initiate a primary Th2 immune response in vivo. J. Exp. Med. 211: 1657-1672.
112. Jacobsen, E. A., K. R. Zellner, D. Colbert, N. A. Lee, and J. J. Lee. 2011. Eosinophils regulate dendritic cells and Th2 pulmonary immune responses following allergen provocation. J. Immunol. 187: 6059-6068.
113. Jin, H. S., Y. Park, C. Elly, and Y.-C. Liu. 2013. Itch expression by Treg cells controls Th2 inflammatory responses. J. Clin. Invest. 123: 4923-4934.
114. Sekiya, T., T. Kondo, T. Shichita, R. Morita, H. Ichinose, and A. Yoshimura. 2015. Suppression of Th2 and Tfh immune reactions by Nr4a receptors in mature T reg cells. J. Exp. Med. 212: 1623-1640.
115. Blair, P. J., S. J. Bultman, J. C. Haas, B. T. Rouse, J. E. Wilkinson, and V. L. Godfrey. 1994. CD4+CD8-T cells are the effector cells in disease pathogenesis in the scurfy (sf) mouse. J. Immunol. 153: 3764-3774.
116. Kanangat, S., P. Blair, R. Reddy, M. Daheshia, V. Godfrey, B. T. Rouse, and E. Wilkinson. 1996. Disease in the scurfy (sf) mouse is associated with overexpression of cytokine genes. Eur. J. Immunol. 26: 161-165.
117. Clark, L. B., M. W. Appleby, M. E. Brunkow, J. E. Wilkinson, S. F. Ziegler, and F. Ramsdell. 1999. Cellular and molecular characterization of the scurfy mouse mutant. J. Immunol. 162: 2546-2554.
118. Chatila, T. A., F. Blaeser, N. Ho, H. M. Lederman, C. Voulgaropoulos, C. Helms, and A. M. Bowcock. 2000. JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome. J. Clin. Invest. 106: R75-R81.
119. Lahl, K., C. T. Mayer, T. Bopp, J. Huehn, C. Loddenkemper, G. Eberl, G.Wirnsberger, K. Dornmair, R. Geffers, E. Schmitt, et al. 2009. Nonfunctional regulatory T cells and defective control of Th2 cytokine production in natural scurfy mutant mice. J. Immunol. 183: 5662-5672.
120. Buzzelli, J. N., H. V. Chalinor, D. I. Pavlic, P. Sutton, T. R. Menheniott, A. S. Giraud, and L. M. Judd. 2015. IL33 is a stomach alarmin that initiates a skewed Th2 response to injury and infection. C. Cell. Mol. Gastroenterol. Hepatol. 1: 203-221.e3. doi:10.1016/j.jcmgh.2014.12.003
121. Sojka, D. K., Y.-H. Huang, and D. J. Fowell. 2008. Mechanisms of regulatory T-cell suppression-a diverse arsenal for a moving target. Immunology 124: 13-22.
122. Walker, L. S. K. 2009. Regulatory T cells overturned: The effectors fight back. Immunology 126: 466-474.
123. D'Alise, A. M., V. Auyeung, M. Feuerer, J. Nishio, J. Fontenot, C. Benoist, and D. Mathis. 2008. The defect in T-cell regulation in NOD mice is an effect on the T-cell effectors. Proc. Natl. Acad. Sci. USA 105: 19857-19862.
124. Gregori, S., N. Giarratana, S. Smiroldo, and L. Adorini. 2003. Dynamics of pathogenic and suppressor T cells in autoimmune diabetes development. J. Immunol. 171: 4040-4047.
125. You, S., M. Belghith, S. Cobbold, M.-A. Alyanakian, C. Gouarin, S. Barriot, C. Garcia, H. Waldmann, J.-F. Bach, and L. Chatenoud. 2005. Autoimmune diabetes onset results from qualitative rather than quantitative age-dependent changes in pathogenic T-cells. Diabetes 54: 1415-1422.
126. Korn, T., J. Reddy, W. Gao, E. Bettelli, A. Awasthi, T. R. Petersen, B. T. Bäckström, R. A. Sobel, K. W. Wucherpfennig, T. B. Strom, et al. 2007. Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation. Nat. Med. 13: 423-431.
127. Monk, C. R., M. Spachidou, F. Rovis, E. Leung, M. Botto, R. I. Lechler, and O. A. Garden. 2005. MRL/Mp CD4+,CD25-T cells show reduced sensitivity to suppression by CD4+,CD25+ regulatory T cells in vitro: A novel defect of T cell regulation in systemic lupus erythematosus. Arthritis Rheum. 52: 1180-1184.
128. Vargas-Rojas, M. I., J. C. Crispín, Y. Richaud-Patin, and J. Alcocer-Varela. 2008. Quantitative and qualitative normal regulatory T cells are not capable of inducing suppression in SLE patients due to T-cell resistance. Lupus 17: 289-294.
129. Venigalla, R. K. C., T. Tretter, S. Krienke, R. Max, V. Eckstein, N. Blank, C. Fiehn, A. D. Ho, and H.-M. Lorenz. 2008. Reduced CD4+,CD25-T cell sensitivity to the suppressive function of CD4+,CD25high,CD127-/low regulatory T cells in patients with active systemic lupus erythematosus. Arthritis Rheum. 58: 2120-2130.
130. Schneider, A., M. Rieck, S. Sanda, C. Pihoker, C. Greenbaum, and J. H. Buckner. 2008. The effector T cells of diabetic subjects are resistant to regulation via CD4+ FOXP3+ regulatory T cells. J. Immunol. 181: 7350-7355.
131. Wehrens, E. J., G. Mijnheer, C. L. Duurland, M. Klein, J. Meerding, J. van Loosdregt, W. de Jager, B. Sawitzki, P. J. Coffer, B. Vastert, et al. 2011. Functional human regulatory T cells fail to control autoimmune inflammation due to PKB/c-akt hyperactivation in effector cells. Blood 118: 3538-3548.
132. Pace, L., S. Rizzo, C. Palombi, F. Brombacher, and G. Doria. 2006. Cutting edge: IL-4-induced protection of CD4+CD25-Th cells from CD4+CD25+ regulatory T cell-mediated suppression. J. Immunol. 176: 3900-3904.
133. Pillemer, B. B. L., Z. Qi, B. Melgert, T. B. Oriss, P. Ray, and A. Ray. 2009. STAT6 activation confers upon T helper cells resistance to suppression by regulatory T cells. J. Immunol. 183: 155-163.
134. Yang, S., N. Fujikado, D. Kolodin, C. Benoist, and D. Mathis. 2015. Immune tolerance. Regulatory T cells generated early in life play a distinct role in maintaining self-tolerance. Science 348: 589-594.
135. Campbell, D. J. 2015. Control of regulatory T cell migration, function, and homeostasis. J. Immunol. 195: 2507-2513.