Human tumor-infiltrating Th17 cells have the capacity to differentiate into IFN-γ+ and FOXP3+ T cells with potent suppressive function

European Journal of Immunology

Volumn 41, Issue 4, 2011, Pages 936-951

  Ye, Jian ^a   Su, Xinming ^a   Hsueh, Eddy C ^a   Zhang, Yanping ^a   Koenig, Joyce M ^a   Hoft, Daniel F ^a   Peng, Guangyong ^a  

^a SAINT LOUIS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

IL 17; T cell development; Th17; Treg

Indexed keywords

GAMMA INTERFERON; INTERLEUKIN 1BETA; INTERLEUKIN 2; INTERLEUKIN 23; INTERLEUKIN 6; OKT 3; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR FOXP3;

ARTICLE; CD4+ CD25+ T LYMPHOCYTE; CELL DIFFERENTIATION; DEMETHYLATION; EPIGENETICS; GENE EXPRESSION; HUMAN; HUMAN CELL; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; SIMULATION; T LYMPHOCYTE; TH17 CELL; TUMOR ASSOCIATED LEUKOCYTE;

CELL DIFFERENTIATION; CELL LINEAGE; CELLS, CULTURED; FORKHEAD TRANSCRIPTION FACTORS; GENE EXPRESSION REGULATION; HUMANS; INTERFERON-GAMMA; LYMPHOCYTES, TUMOR-INFILTRATING; RECEPTORS, ANTIGEN, T-CELL; T-LYMPHOCYTES, REGULATORY; TH17 CELLS;

EID: 79953045621     PISSN: 00142980     EISSN: 15214141     Source Type: Journal    
DOI: 10.1002/eji.201040682     Document Type: Article

References (61)

1. Bettelli, E., Korn, T. and Kuchroo, V. K., Th17: the third member of the effector T cell trilogy. Curr. Opin. Immunol. 2007. 19: 652-657.
2. Steinman, L., A brief history of T(H)17, the first major revision in the T(H)1/T(H)2 hypothesis of T cell-mediated tissue damage. Nat. Med. 2007. 13: 139-145.
3. Wing, K. and Sakaguchi, S., Regulatory T cells exert checks and balances on self tolerance and autoimmunity. Nat. Immunol. 2010. 11: 7-13.
4. Shevach, E. M., CD4+CD25+suppressor T cells: more questions than answers. Nat. Rev. Immunol. 2002. 2: 389-400.
5. Tesmer, L. A., Lundy, S. K., Sarkar, S. and Fox, D. A., Th17 cells in human disease. Immunol. Rev. 2008. 223: 87-113.
6. Weaver, C. T., Harrington, L. E., Mangan, P. R., Gavrieli, M. and Murphy, K. M., Th17: an effector CD4 T cell lineage with regulatory T cell ties. Immunity 2006. 24: 677-688.
7. Zhou, L., Chong, M. M. and Littman, D. R., Plasticity of CD4+T cell lineage differentiation. Immunity 2009. 30: 646-655.
8. Dong, C., TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat. Rev. Immunol. 2008. 8: 337-348.
9. Chen, Q., Yang, W., Gupta, S., Biswas, P., Smith, P., Bhagat, G. and Pernis, A. B., IRF-4-binding protein inhibits interleukin-17 and interleukin-21 production by controlling the activity of IRF-4 transcription factor. Immunity 2008. 29: 899-911.
10. Ivanov, I. I., McKenzie, B. S., Zhou, L., Tadokoro, C. E., Lepelley, A., Lafaille, J. J., Cua, D. J. and Littman, D. R., The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+T helper cells. Cell 2006. 126: 1121-1133.
11. Korn, T., Bettelli, E., Gao, W., Awasthi, A., Jager, A., Strom, T. B., Oukka, M. and Kuchroo, V. K., IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature 2007. 448: 484-487.
12. Mangan, P. R., Harrington, L. E., O'Quinn, D. B., Helms, W. S., Bullard, D. C., Elson, C. O., Hatton, R. D. et al., Transforming growth factor-beta induces development of the T(H)17 lineage. Nature 2006. 441: 231-234.
13. Zhou, L., Ivanov, I. I., Spolski, R., Min, R., Shenderov, K., Egawa, T., Levy, D. E. et al., IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat. Immunol. 2007. 8: 967-974.
14. McGeachy, M. J., Bak-Jensen, K. S., Chen, Y., Tato, C. M., Blumenschein, W., McClanahan, T. and Cua, D. J., TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nat. Immunol. 2007. 8: 1390-1397.
15. Cua, D. J., Sherlock, J., Chen, Y., Murphy, C. A., Joyce, B., Seymour, B., Lucian, L. et al., Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 2003. 421: 744-748.
16. Josefowicz, S. Z. and Rudensky, A., Control of regulatory T cell lineage commitment and maintenance. Immunity 2009. 30: 616-625.
17. Rowell, E. and Wilson, C. B., Programming perpetual T helper cell plasticity. Immunity 2009. 30: 7-9.
18. Lee, Y. K., Mukasa, R., Hatton, R. D. and Weaver, C. T., Developmental plasticity of Th17 and Treg cells. Curr. Opin. Immunol. 2009. 21: 274-280.
19. Annunziato, F., Cosmi, L., Santarlasci, V., Maggi, L., Liotta, F., Mazzinghi, B., Parente, E. et al., Phenotypic and functional features of human Th17 cells. J. Exp. Med. 2007. 204: 1849-1861.
20. Annunziato, F. and Romagnani, S., Do studies in humans better depict Th17 cells? Blood 2009. 114: 2213-2219.
21. Lee, Y. K., Turner, H., Maynard, C. L., Oliver, J. R., Chen, D., Elson, C. O. and Weaver, C. T., Late developmental plasticity in the T helper 17 lineage. Immunity 2009. 30: 92-107.
22. Bending, D., De La Pena, H., Veldhoen, M., Phillips, J. M., Uyttenhove, C., Stockinger, B. and Cooke, A., Highly purified Th17 cells from BDC2.5NOD mice convert into Th1-like cells in NOD/SCID recipient mice. J. Clin. Invest. 2009. 1119: 565-572.
23. Wan, Y. Y. and Flavell, R. A., Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression. Nature 2007. 445: 766-770.
24. Koenen, H. J., Smeets, R. L., Vink, P. M., van Rijssen, E., Boots, A. M. and Joosten, I., Human CD25highFoxp3pos regulatory T cells differentiate into IL-17-producing cells. Blood 2008. 112: 2340-2352.
25. Voo, K. S., Wang, Y. H., Santori, F. R., Boggiano, C., Arima, K., Bover, L., Hanabuchi, S. et al., Identification of IL-17-producing FOXP3+regulatory T cells in humans. Proc. Natl. Acad. Sci. USA 2009. 106: 4793-4798.
26. Miyahara, Y., Odunsi, K., Chen, W., Peng, G., Matsuzaki, J. and Wang, R. F., Generation and regulation of human CD4+IL-17-producing T cells in ovarian cancer. Proc. Natl. Acad. Sci. USA 2008. 105: 15505-15510.
27. Su, X., Ye, J., Hsueh, E. C., Zhang, Y., Hoft, D. F. and Peng, G., Tumor microenvironments direct the recruitment and expansion of human Th17 cells. J. Immunol. 2010, 184: 1630-1641.
28. Peng, G., Wang, H. Y., Peng, W., Kiniwa, Y., Seo, K. H. and Wang, R. F., Tumor-infiltrating gammadelta T cells suppress T and dendritic cell function via mechanisms controlled by a unique toll-like receptor signaling pathway. Immunity 2007. 27: 334-348.
29. Wang, H. Y., Lee, D. A., Peng, G., Guo, Z., Li, Y., Kiniwa, Y., Shevach, E. M. and Wang, R. F., Tumor-specific human CD4+regulatory T cells and their ligands: implications for immunotherapy. Immunity 2004. 20: 107-118.
30. McKee, M. D., Clay, T. M., Diamond, R. A., Rosenberg, S. A. and Nishimura, M. I., Quantitation of T-cell receptor frequencies by competitive polymerase chain reaction: dynamics of T-cell clonotype frequencies in an expanding tumor-infiltrating lymphocyte culture. J. Immunother. 2000. 23: 419-429.
31. Sato, W., Aranami, T. and Yamamura, T., Cutting edge: human Th17 cells are identified as bearing CCR2+CCR5- phenotype. J. Immunol. 2007. 178: 7525-7529.
32. Singh, S. P., Zhang, H. H., Foley, J. F., Hedrick, M. N. and Farber, J. M., Human T cells that are able to produce IL-17 express the chemokine receptor CCR6. J. Immunol. 2008. 180: 214-221.
33. Liu, H. and Rohowsky-Kochan, C., Regulation of IL-17 in human CCR6+effector memory T cells. J. Immunol. 2008. 180: 7948-7957.
34. Acosta-Rodriguez, E. V., Rivino, L., Geginat, J., Jarrossay, D., Gattorno, M., Lanzavecchia, A., Sallusto, F. and Napolitani, G., Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat. Immunol. 2007. 8: 639-646.
35. Wilson, N. J., Boniface, K., Chan, J. R., McKenzie, B. S., Blumenschein, W. M., Mattson, J. D., Basham, B. et al., Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat. Immunol. 2007. 8: 950-957.
36. Pene, J., Chevalier, S., Preisser, L., Venereau, E., Guilleux, M. H., Ghannam, S., Moles, J. P. et al., Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes. J. Immunol. 2008, 180: 7423-7430.
37. McGeachy, M. J., Chen, Y., Tato, C. M., Laurence, A., Joyce-Shaikh, B., Blumenschein, W. M., McClanahan, T. K. et al., The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat. Immunol. 2009. 10: 314-324.
38. Lim, H. W., Lee, J., Hillsamer, P. and Kim, C. H., Human Th17 cells share major trafficking receptors with both polarized effector T cells and FOXP3+regulatory T cells. J. Immunol. 2008. 180: 122-129.
39. Peng, G., Guo, Z., Kiniwa, Y., Voo, K. S., Peng, W., Fu, T., Wang, D. Y. et al., Toll-like receptor 8-mediated reversal of CD4+regulatory T cell function. Science 2005. 309: 1380-1384.
40. Morgan, R. A., Dudley, M. E., Wunderlich, J. R., Hughes, M. S., Yang, J. C., Sherry, R. M., Royal, R. E. et al., Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 2006. 314: 126-129.
41. Floess, S., Freyer, J., Siewert, C., Baron, U., Olek, S., Polansky, J., Schlawe, K. et al., Epigenetic control of the foxp3 locus in regulatory T cells. PLoS Biol. 2007. 5: e38.
42. Pillai, V., Ortega, S. B., Wang, C. K. and Karandikar, N. J., Transient regulatory T-cells: a state attained by all activated human T-cells. Clin. Immunol. 2007. 123: 18-29.
43. Baron, U., Floess, S., Wieczorek, G., Baumann, K., Grutzkau, A., Dong, J., Thiel, A. et al., DNA demethylation in the human FOXP3 locus discriminates regulatory T cells from activated FOXP3(+) conventional T cells. Eur. J. Immunol. 2007. 37: 2378-2389.
44. Nagar, M., Vernitsky, H., Cohen, Y., Dominissini, D., Berkun, Y., Rechavi, G., Amariglio, N. and Goldstein, I., Epigenetic inheritance of DNA methylation limits activation-induced expression of FOXP3 in conventional human CD25-CD4+T cells. Int. Immunol. 2008. 20: 1041-1055.
45. Wieczorek, G., Asemissen, A., Model, F., Turbachova, I., Floess, S., Liebenberg, V., Baron, U. et al. Quantitative DNA methylation analysis of FOXP3 as a new method for counting regulatory T cells in peripheral blood and solid tissue. Cancer Res. 2009. 69: 599-608.
46. Gocke, A. R., Cravens, P. D., Ben, L. H., Hussain, R. Z., Northrop, S. C., Racke, M. K. and Lovett-Racke, A. E., T-bet regulates the fate of Th1 and Th17 lymphocytes in autoimmunity. J. Immunol. 2007. 178: 1341-1348.
47. Jurgens, B., Hainz, U., Fuchs, D., Felzmann, T. and Heitger, A., Interferon-gamma-triggered indoleamine 2, 3-dioxygenase competence in human monocyte-derived dendritic cells induces regulatory activity in allogeneic T cells. Blood 2009. 114: 3235-3243.
48. Zhu, L., Ji, F., Wang, Y., Zhang, Y., Liu, Q., Zhang, J. Z., Matsushima, K. and Cao, Q., Synovial autoreactive T cells in rheumatoid arthritis resist IDO-mediated inhibition. J. Immunol. 2006. 177: 8226-8233.
49. Pandiyan, P., Zheng, L., Ishihara, S., Reed, J. and Lenardo, M. J., CD4+CD25+Foxp3+regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+T cells. Nat. Immunol. 2007. 8: 1353-1362.
50. Thornton, A. M. and Shevach, E. M., CD4+CD25+immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J. Exp. Med. 1998. 188: 287-296.
51. Acosta-Rodriguez, E. V., Napolitani, G., Lanzavecchia, A. and Sallusto, F., Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nat. Immunol. 2007. 8: 942-949.
52. Beriou, G., Costantino, C. M., Ashley, C. W., Yang, L., Kuchroo, V. K., Baecher-Allan, C. and Hafler, D. A., IL-17 producing human peripheral regulatory T cells retain suppressive function. Blood 2009. 113: 4240-4249.
53. Deknuydt, F., Bioley, G., Valmori, D. and Ayyoub, M., IL-1beta and IL-2 convert human Treg into T(H)17 cells. Clin. Immunol. 2009. 131: 298-307.
54. Yang, X. O., Nurieva, R., Martinez, G. J., Kang, H. S., Chung, Y., Pappu, B. P., Shah, B. et al., Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity 2008. 29: 44-56.
55. Zheng, S. G., Wang, J. and Horwitz, D. A., Cutting edge: Foxp3+CD4+CD25+regulatory T cells induced by IL-2 and TGF-beta are resistant to Th17 conversion by IL-6. J. Immunol. 2008. 180: 7112-7116.
56. Wei, G., Wei, L., Zhu, J., Zang, C., Hu-Li, J., Yao, Z., Cui, K. et al., Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+T cells. Immunity 2009. 30: 155-167.
57. Huehn, J., Polansky, J. K. and Hamann, A., Epigenetic control of FOXP3 expression: the key to a stable regulatory T-cell lineage? Nat. Rev. Immunol. 2009. 9: 83-89.
58. Oldenhove, G., Bouladoux, N., Wohlfert, E. A., Hall, J. A., Chou, D., Dos Santos, L., O'Brien, S. et al., Decrease of Foxp3+Treg cell number and acquisition of effector cell phenotype during lethal infection. Immunity 2009. 31: 772-786.
59. Sharma, M. D., Hou, D. Y., Liu, Y., Koni, P. A., Metz, R., Chandler, P., Mellor, A. L. et al., Indoleamine 2, 3-dioxygenase controls conversion of Foxp3+Tregs to TH17-like cells in tumor-draining lymph nodes. Blood 2009. 113: 6102-6111.
60. Kim, M. S., Yamashita, K., Baek, J. H., Park, H. L., Carvalho, A. L., Osada, M., Hoque, M. O. et al., N-methyl-D-aspartate receptor type 2B is epigenetically inactivated and exhibits tumor-suppressive activity in human esophageal cancer. Cancer Res. 2006. 66: 3409-3418.
61. Manel, N., Unutmaz, D. and Littman, D. R., The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction of the nuclear receptor RORgammat. Nat. Immunol. 2008. 9: 641-649.