CD8 regulates T regulatory cell production of IL-6 and maintains their suppressive phenotype in allergic lung disease

Journal of Immunology

Volumn 186, Issue 1, 2011, Pages 113-120

  Joetham, Anthony ^a   Okamoto, Masakazu ^a   Takeda, Katsuyuki ^a   Schedel, Michaela ^a   Ohnishi, Hiroshi ^a   Dakhama, Azzeddine ^a   Gelfand, Erwin W ^a  

^a DEPARTMENT OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD8 ANTIGEN; INTERLEUKIN 10; INTERLEUKIN 6; INTERLEUKIN 6 ANTIBODY; INTERLEUKIN 6 RECEPTOR ALPHA ANTIBODY; RECEPTOR ANTIBODY; TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG;

ADOPTIVE TRANSFER; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CD4+ CD25+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELLULAR IMMUNITY; CONTROLLED STUDY; CYTOKINE PRODUCTION; FEMALE; IMMUNOREGULATION; MOUSE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; RESPIRATORY TRACT ALLERGY; RESPIRATORY TRACT INFLAMMATION; WILD TYPE;

ANIMALS; ANTIGENS, CD8; CELLS, CULTURED; FEMALE; FORKHEAD TRANSCRIPTION FACTORS; IMMUNOPHENOTYPING; IMMUNOSUPPRESSION; INTERLEUKIN-10; INTERLEUKIN-6; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; RECEPTORS, INTERLEUKIN-6; RESPIRATORY HYPERSENSITIVITY; T-LYMPHOCYTES, REGULATORY; TRANSFORMING GROWTH FACTOR BETA;

EID: 79251592529     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1001663     Document Type: Article

References (33)

1. 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.
2. Williams, L. M., and A. Y. Rudensky. 2007. Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3. Nat. Immunol. 8: 277-284.
3. 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.
4. 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.
5. 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.
6. 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.
7. Hawrylowicz, C. M., and A. O'Garra. 2005. Potential role of interleukin-10-secreting regulatory T cells in allergy and asthma. Nat. Rev. Immunol. 5: 271-283.
8. Lewkowich, I. P., N. S. Herman, K. W. Schleifer, M. P. Dance, B. L. Chen, K. M. Dienger, A. A. Sproles, J. S. Shah, J. Köhl, Y. Belkaid, and M. Wills-Karp. 2005. CD4+CD25+ T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function. J. Exp. Med. 202: 1549-1561.
9. Kearley, J., J. E. Barker, D. S. Robinson, and C. M. Lloyd. 2005. Resolution of airway inflammation and hyperreactivity after in vivo transfer of CD4+CD25+ regulatory T cells is interleukin 10 dependent. J. Exp. Med. 202: 1539-1547.
10. Joetham, A., K. Takeda, C. Taube, N. Miyahara, S. Matsubara, T. Koya, Y. H. Rha, A. Dakhama, and E. W. Gelfand. 2007. Naturally occurring lung CD4 (+)CD25(+) T cell regulation of airway allergic responses depends on IL-10 induction of TGF-β. J. Immunol. 178: 1433-1442.
11. Joetham, A., K. Takeda, N. Miyahara, S. Matsubara, H. Ohnishi, T. Koya, A. Dakhama, and E. W. Gelfand. 2007. Activation of naturally occurring lung CD4(+)CD25(+) regulatory T cells requires CD8 and MHC I interaction. Proc. Natl. Acad. Sci. USA 104: 15057-15062.
12. Joetham, A., S. Matsubara, M. Okamoto, K. Takeda, N. Miyahara, A. Dakhama, and E. W. Gelfand. 2008. Plasticity of naturally occurring regulatory T cells: subversion of suppressive function and conversion to enhancement of lung allergic responses. J. Immunol. 180: 7117-7124.
13. 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.
14. Presser, K., D. Schwinge, M. Wegmann, S. Huber, S. Schmitt, A. Quaas, J. H. Maxeiner, S. Finotto, A. W. Lohse, M. Blessing, and C. Schramm. 2008. Coexpression of TGF-β1 and IL-10 enables regulatory T cells to completely suppress airway hyperreactivity. J. Immunol. 181: 7751-7758.
15. Joetham, A., K. Takeda, M. Okamoto, C. Taube, H. Matsuda, A. Dakhama, and E. W. Gelfand. 2009. Antigen-specificity is not required for naturally occurring regulatory T cell modulation of lung allergic responses. J. Immunol. 183: 1821-1827.
16. Zhou, X., S. L. Bailey-Bucktrout, L. T. Jeker, C. Penaranda, M. Martínez-Llordella, M. Ashby, M. Nakayama, W. Rosenthal, and J. A. Bluestone. 2009. Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo. Nat. Immunol. 10: 1000-1007.
17. Pasare, C., and R. Medzhitov. 2003. Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science 299: 1033-1036.
18. Wan, S., C. Xia, and L. Morel. 2007. IL-6 produced by dendritic cells from lupus-prone mice inhibits CD4+CD25+ T cell regulatory functions. J. Immunol. 178: 271-279. (Pubitemid 46033610)
19. Yang, X. O., R. Nurieva, G. J. Martinez, H. S. Kang, Y. Chung, B. P. Pappu, B. Shah, S. H. Chang, K. S. Schluns, S. S. Watowich, et al. 2008. Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity 29: 44-56.
20. Lal, G., N. Zhang, W. van der Touw, Y. Ding, W. Ju, E. P. Bottinger, S. P. Reid, D. E. Levy, and J. S. Bromberg. 2009. Epigenetic regulation of Foxp3 expression in regulatory T cells by DNA methylation. J. Immunol. 182: 259-273.
21. Doganci, A., T. Eigenbrod, N. Krug, G. T. De Sanctis, M. Hausding, V. J. Erpenbeck, B. Haddad, H. A. Lehr, E. Schmitt, T. Bopp, et al. 2005. The IL-6R alpha chain controls lung CD4+CD25+ Treg development and function during allergic airway inflammation in vivo. J. Clin. Invest. 115: 313-325.
22. Takeda, K., E. Hamelmann, A. Joetham, L. D. Shultz, G. L. Larsen, C. G. Irvin, and E. W. Gelfand. 1997. Development of eosinophilic airway inflammation and airway hyperresponsiveness in mast cell-deficient mice. J. Exp. Med. 186: 449-454.
23. Miyahara, N., K. Takeda, S. Miyahara, C. Taube, A. Joetham, T. Koya, S. Matsubara, A. Dakhama, A. M. Tager, A. D. Luster, and E. W. Gelfand. 2005. Leukotriene B4 receptor-1 is essential for allergen-mediated recruitment of CD8+ T cells and airway hyperresponsiveness. J. Immunol. 174: 4979-4984.
24. Okamoto, M., K. Takeda, A. Joetham, H. Ohnishi, H. Matsuda, C. H. Swasey, B. J. Swanson, K. Yasutomo, A. Dakhama, and E. W. Gelfand. 2008. Essential role of Notch signaling in effector memory CD8+ T cell-mediated airway hyperresponsiveness and inflammation. J. Exp. Med. 205: 1087-1097.
25. Miyahara, N., H. Ohnishi, H. Matsuda, S. Miyahara, K. Takeda, T. Koya, S. Matsubara, M. Okamoto, A. Dakhama, B. Haribabu, and E. W. Gelfand. 2008. Leukotriene B4 receptor 1 expression on dendritic cells is required for the development of Th2 responses and allergen-induced airway hyperresponsiveness. J. Immunol. 181: 1170-1178.
26. Sakaguchi, S., T. Yamaguchi, T. Nomura, and M. Ono. 2008. Regulatory T cells and immune tolerance. Cell 133: 775-787.
27. Hori, S., T. Nomura, and S. Sakaguchi. 2003. Control of regulatory T cell development by the transcription factor Foxp3. Science 299: 1057-1061. (Pubitemid 36222930)
28. + regulatory T cells. Nat. Immunol. 4: 330-336.
29. Sharabi, A., and E. Mozes. 2008. The suppression of murine lupus by a tolerogenic peptide involves foxp3-expressing CD8 cells that are required for the optimal induction and function of foxp3-expressing CD4 cells. J. Immunol. 181: 3243-3251.
30. Yamazaki, S., D. Dudziak, G. F. Heidkamp, C. Fiorese, A. J. Bonito, K. Inaba, M. C. Nussenzweig, and R. M. Steinman. 2008. CD8+ CD205+ splenic dendritic cells are specialized to induce Foxp3+ regulatory T cells. J. Immunol. 181: 6923-6933.
31. Naka, T., N. Nishimoto, and T. Kishimoto. 2002. The paradigm of IL-6: from basic science to medicine. Arthritis Res. 4(Suppl. 3): S233-S242.
32. Zheng, S. G., J. Wang, and D. A. Horwitz. 2008. Cutting edge: Foxp3+CD4+CD25+ regulatory T cells induced by IL-2 and TGF-β are resistant to Th17 conversion by IL-6. J. Immunol. 180: 7112-7116.
33. von Boehmer, H. 2005. Mechanisms of suppression by suppressor T cells. Nat. Immunol. 6: 338-344.