CCR6 is expressed on an IL-10-producing, autoreactive memory T cell population with context-dependent regulatory function

Journal of Experimental Medicine

Volumn 207, Issue 3, 2010, Pages 565-577

  Rivino, Laura ^a,b,e   Gruarin, Paola ^c   Häringer, Barbara ^b   Steinfelder, Svenja ^b   Lozza, Laura ^a,b   Steckel, Bodo ^b   Weick, Anja ^b   Sugliano, Elisa ^c   Jarrossay, David ^a   Kühl, Anja A ^b   Loddenkemper, Christoph ^b,d   Abrignani, Sergio ^c   Sallusto, Federica ^a   Lanzavecchia, Antonio ^a   Geginat, Jens ^a,b,c  

^a INSTITUTE FOR RESEARCH IN BIOMEDICINE   (Switzerland)

^b CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^c Istituto Nazionale di Genetica Molecolare   (Italy)

^d TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^e NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

Author keywords

[No Author keywords available]

Indexed keywords

CD3 ANTIBODY; CD40 LIGAND; CHEMOKINE RECEPTOR CCR6; GAMMA INTERFERON; INTERLEUKIN 10; INTERLEUKIN 17; INTERLEUKIN 2; MACROPHAGE INFLAMMATORY PROTEIN 3ALPHA; T LYMPHOCYTE RECEPTOR; TETANUS TOXOID; TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA;

ANTIGEN EXPRESSION; ANTIGEN RECOGNITION; ARTICLE; AUTOIMMUNITY; CD4+ T LYMPHOCYTE; CELL INTERACTION; CELL ISOLATION; CELL PROLIFERATION; CONTROLLED STUDY; CYTOKINE PRODUCTION; DENDRITIC CELL; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNE RESPONSE; IMMUNOHISTOCHEMISTRY; IMMUNOPATHOLOGY; IMMUNOSTIMULATION; LYMPHOCYTE CLONE; MEMORY T LYMPHOCYTE; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SPLEEN; T LYMPHOCYTE SUBPOPULATION;

CD4-POSITIVE T-LYMPHOCYTES; GENE EXPRESSION REGULATION; HOMEOSTASIS; HUMANS; IMMUNOLOGIC MEMORY; IMMUNOSUPPRESSION; INTERFERON-GAMMA; INTERLEUKIN-10; INTERLEUKIN-2; RECEPTORS, ANTIGEN, T-CELL; RECEPTORS, CCR6; T-LYMPHOCYTES; T-LYMPHOCYTES, REGULATORY; TRANSFORMING GROWTH FACTOR BETA;

EID: 77949511548     PISSN: 00221007     EISSN: 15409538     Source Type: Journal    
DOI: 10.1084/jem.20091021     Document Type: Article

References (58)

1. Acosta-Rodriguez, E.V., L. Rivino, J. Geginat, D. Jarrossay, M. Gattorno, A. Lanzavecchia, F. Sallusto, and G. Napolitani. 2007. Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat. Immunol. 8:639-646. doi:10.1038/ni1467
2. - Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis. J. Exp. Med. 204:285-297. doi:10.1084/jem.20061886
3. Annunziato, F., L. Cosmi, V. Santarlasci, L. Maggi, F. Liotta, B. Mazzinghi, E. Parente, L. Filì, S. Ferri, F. Frosali, et al. 2007. Phenotypic and functional features of human Th17 cells. J. Exp. Med. 204:1849-1861. doi:10 .1084/jem.20070663
4. Apostolou, I., and H. von Boehmer. 2004. In vivo instruction of suppressor commitment in naive T cells. J. Exp. Med. 199:1401-1408. doi:10 .1084/jem.20040249
5. Asseman, C., S. Mauze, M.W. Leach, R.L. Coffman, and F. Powrie. 1999. An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. J. Exp. Med. 190:995-1004. doi:10.1084/jem.190.7.995
6. + T cell activation response that results in secretion of immunomodulatory cytokines and apoptosis. J. Exp. Med. 191:651-660. doi:10.1084/jem.191.4.651
7. Bluestone, J.A., and A.K. Abbas. 2003. Natural versus adaptive regulatory T cells. Nat. Rev. Immunol. 3:253-257. doi:10.1038/nri1032
8. Brocker, T. 1997. Survival of mature CD4 T lymphocytes is dependent on major histocompatibility complex class II-expressing dendritic cells. J. Exp. Med. 186:1223-1232. doi:10.1084/jem.186.8.1223
9. Cai, G., and D.A. Hafler. 2007. Multispecific responses by T cells expanded by endogenous self-peptide/MHC complexes. Eur. J. Immunol. 37:602-612. doi:10.1002/eji.200636787
10. Cook, D.N., D.M. Prosser, R. Forster, J. Zhang, N.A. Kuklin, S.J. Abbondanzo, X.D. Niu, S.C. Chen, D.J. Manfra, M.T. Wiekowski, et al. 2000. CCR6 mediates dendritic cell localization, lymphocyte homeostasis, and immune responses in mucosal tissue. Immunity. 12: 495-503. doi:10.1016/S1074- 7613(00)80201-0
11. Couper, K.N., D.G. Blount, M.S. Wilson, J.C. Hafalla, Y. Belkaid, M. Kamanaka, R.A. Flavell, J.B. de Souza, and E.M. Riley. 2008. IL-10 from CD4CD25Foxp3CD127 adaptive regulatory T cells modulates parasite clearance and pathology during malaria infection. PLoS Pathog. 4:e1000004. doi:10.1371/journal.ppat.1000004
12. + T cell memory by promoting the generation of IL-7Rα-expressing cells. J. Exp. Med. 204:547-557. doi:10.1084/jem.20062381
13. +CD25- T cells through Foxp3 induction and downregulation of Smad7. J. Immunol. 172:5149-5153.
14. Gett, A.V., F. Sallusto, A. Lanzavecchia, and J. Geginat. 2003. T cell fitness determined by signal strength. Nat. Immunol. 4:355-360. doi:10.1038/ni908
15. + T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature. 389:737-742. doi:10.1038/39614
16. + CTL. J. Immunol. 159:3748-3756.
17. Häringer, B., L. Lozza, B. Steckel, and J. Geginat. 2009. Identification and characterization of IL-10/IFN-γ-producing effector-like T cells with regulatory function in human blood. J. Exp. Med. 206:1009-1017. doi:10.1084/jem.20082238
18. Herbst, H., H.D. Foss, J. Samol, I. Araujo, H. Klotzbach, H. Krause, A. Agathanggelou, G. Niedobitek, and H. Stein. 1996. Frequent expression of interleukin-10 by Epstein-Barr virus-harboring tumor cells of Hodgkin's disease. Blood. 87:2918-2929.
19. Homey, B., M.C. Dieu-Nosjean, A. Wiesenborn, C. Massacrier, J.J. Pin, E. Oldham, D. Catron, M.E. Buchanan, A. Müller, R. deWaal Malefyt, et al. 2000. Up-regulation of macrophage inflammatory protein-3 alpha/CCL20 and CC chemokine receptor 6 in psoriasis. J. Immunol. 164:6621-6632.
20. Hutloff, A., A.M. Dittrich, K.C. Beier, B. Eljaschewitsch, R. Kraft, I. Anagnostopoulos, and R.A. Kroczek. 1999. ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28. Nature. 397:263-266. doi:10.1038/16717
21. - Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infection. J. Exp. Med. 204:273-283. doi:10.1084/jem.20062175
22. + T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J. Exp. Med. 192:1213-1222. doi:10.1084/jem.192.9. 1213
23. Jordan, M.S., A. Boesteanu, A.J. Reed, A.L. Petrone, A.E. Holenbeck, M.A. Lerman, A. Naji, and A.J. Caton. 2001. Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nat. Immunol. 2:301-306. doi:10.1038/86302
24. Kaser, A., O. Ludwiczek, S. Holzmann, A.R. Moschen, G. Weiss, B. Enrich, I. Graziadei, S. Dunzendorfer, C.J. Wiedermann, E. Mürzl, et al. 2004. Increased expression of CCL20 in human inflammatory bowel disease. J. Clin. Immunol. 24:74-85. doi:10.1023/B:JOCI.0000018066.46279.6b
25. Kassiotis, G., S. Garcia, E. Simpson, and B. Stockinger. 2002. Impairment of immunological memory in the absence of MHC despite survival of memory T cells. Nat. Immunol. 3:244-250. doi:10.1038/ni766
26. Kitani, A., K. Chua, K. Nakamura, and W. Strober. 2000. Activated self-MHC-reactive T cells have the cytokine phenotype of Th3/T regulatory cell 1 T cells. J. Immunol. 165:691-702.
27. Kleinewietfeld, M., F. Puentes, G. Borsellino, L. Battistini, O. Rötzschke, and K. Falk. 2005. CCR6 expression defines regulatory effector/memory-like cells within the CD25(+)CD4+ T-cell subset. Blood. 105:2877-2886. doi:10.1182/blood-2004-07-2505
28. Kyewski, B., and L. Klein. 2006. A central role for central tolerance. Annu. Rev. Immunol. 24:571-606. doi:10.1146/annurev.immunol.23.021704. 115601
29. Lanzavecchia, A., and F. Sallusto. 2002. Progressive differentiation and selection of the fittest in the immune response. Nat. Rev. Immunol. 2:982-987. doi:10.1038/nri959
30. Lukacs, N.W., D.M. Prosser, M. Wiekowski, S.A. Lira, and D.N. Cook. 2001. Requirement for the chemokine receptor CCR6 in allergic pulmonary inflammation. J. Exp. Med. 194:551-555. doi:10.1084/jem.194.4.551
31. Maloy, K.J., and F. Powrie. 2001. Regulatory T cells in the control of immune pathology. Nat. Immunol. 2:816-822. doi:10.1038/ni0901-816
32. Matsui, T., T. Akahoshi, R. Namai, A. Hashimoto, Y. Kurihara, M. Rana, A. Nishimura, H. Endo, H. Kitasato, S. Kawai, et al. 2001. Selective recruitment of CCR6-expressing cells by increased production of MIP-3 alpha in rheumatoid arthritis. Clin. Exp. Immunol. 125:155-161. doi:10.1046/j.1365-2249.2001. 01542.x
33. Maynard, C.L., L.E. Harrington, K.M. Janowski, J.R. Oliver, C.L. Zindl, A.Y. Rudensky, and C.T. Weaver. 2007. Regulatory T cells expressing interleukin 10 develop from Foxp3+ and Foxp3- precursor cells in the absence of interleukin 10. Nat. Immunol. 8:931-941. doi:10.1038/ni1504
34. Moore, K.W., R. de Waal Malefyt, R.L. Coffman, and A. O'Garra. 2001. Interleukin-10 and the interleukin-10 receptor. Annu. Rev. Immunol. 19:683-765. doi:10.1146/annurev.immunol.19.1.683
35. + T cells are hyperreactive to antigenic challenge in vitro. J. Exp. Med. 184:2141-2151. doi:10.1084/jem.184.6. 2141
36. Ramsey, C., S. Hässler, P. Marits, O. Kämpe, C.D. Surh, L. Peltonen, and O. Winqvist. 2006. Increased antigen presenting cell-mediated T cell activation in mice and patients without the autoimmune regulator. Eur. J. Immunol. 36:305-317. doi:10.1002/eji.200535240
37. + central memory T cells. J. Exp. Med. 200:725-735. doi:10.1084/jem.20040774
38. Roers, A., L. Siewe, E. Strittmatter, M. Deckert, D. Schlüter, W. Stenzel, A.D. Gruber, T. Krieg, K. Rajewsky, and W. Müller. 2004. T cell-specific inactivation of the interleukin 10 gene in mice results in enhanced T cell responses but normal innate responses to lipopolysaccharide or skin irritation. J. Exp. Med. 200:1289-1297. doi:10.1084/jem.20041789
39. Roncarolo, M.G., and M.K. Levings. 2000. The role of different subsets of T regulatory cells in controlling autoimmunity. Curr. Opin. Immunol. 12:676-683. doi:10.1016/S0952-7915(00)00162-X
40. Ruth, J.H., S. Shahrara, C.C. Park, J.C. Morel, P. Kumar, S. Qin, and A.E. Koch. 2003. Role of macrophage inflammatory protein-3alpha and its ligand CCR6 in rheumatoid arthritis. Lab. Invest. 83:579-588.
41. 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. doi:10.1146/annurev.immunol .21.120601.141122
42. Scheffold, A., J. Hühn, and T. Höfer. 2005. Regulation of CD4+CD25+ regulatory T cell activity: it takes (IL-)two to tango. Eur. J. Immunol. 35:1336-1341. doi:10.1002/eji.200425887
43. Schutyser, E., S. Struyf, and J. Van Damme. 2003. The CC chemokine CCL20 and its receptor CCR6. Cytokine Growth Factor Rev. 14:409-426. doi:10.1016/S1359-6101(03)00049-2
44. Schwartz, R.H. 1997. T cell clonal anergy. Curr. Opin. Immunol. 9:351-357. doi:10.1016/S0952-7915(97)80081-7
45. Seddon, B., and D. Mason. 1999. Peripheral autoantigen induces regulatory T cells that prevent autoimmunity. J. Exp. Med. 189:877-882. doi:10.1084/jem.189.5.877
46. + suppressor T cells. J. Exp. Med. 193:F41-F46. doi:10.1084/jem.193.11.F41
47. Stefanová, I., J.R. Dorfman, and R.N. Germain. 2002. Self-recognition promotes the foreign antigen sensitivity of naive T lymphocytes. Nature. 420:429-434. doi:10.1038/nature01146
48. Steinman, R.M., and M.C. Nussenzweig. 2002. Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc. Natl. Acad. Sci. USA. 99:351-358. doi:10.1073/pnas.231606698
49. Uhlig, H.H., J. Coombes, C. Mottet, A. Izcue, C. Thompson, A. Fanger, A. Tannapfel, J.D. Fontenot, F. Ramsdell, and F. Powrie. 2006. Characterization of Foxp3+CD4+CD25+ and IL-10-secreting CD4+CD25+ T cells during cure of colitis. J. Immunol. 177 :5852-5860.
50. Valitutti, S., S. Müller, M. Dessing, and A. Lanzavecchia. 1996. Different responses are elicited in cytotoxic T lymphocytes by different levels of T cell receptor occupancy. J. Exp. Med. 183:1917-1921. doi:10.1084/jem.183.4.1917
51. Vanbervliet, B., B. Homey, I. Durand, C. Massacrier, S. Aït-Yahia, O. de Bouteiller, A. Vicari, and C. Caux. 2002. Sequential involvement of CCR2 and CCR6 ligands for immature dendritic cell recruitment: possible role at inflamed epithelial surfaces. Eur. J. Immunol. 32:231-242. doi:10.1002/1521-4141(200201)32:1〈231:: AID-IMMU231〉3.0.CO;2-8
52. van den Boorn, J.G., I.C. Le Poole, and R.M. Luiten. 2006. T-cell avidity and tuning: the flexible connection between tolerance and autoimmunity. Int. Rev. Immunol. 25:235-258. doi:10.1080/08830180600743081
53. Varona, R., R. Villares, L. Carramolino, I. Goya, A. Zaballos, J. Gutiérrez, M. Torres, C. Martínez-A, and G. Márquez. 2001. CCR6-deficient mice have impaired leukocyte homeostasis and altered contact hypersensitivity and delayed-type hypersensitivity responses. J. Clin. Invest. 107:R37-R45. doi:10.1172/JCI11297
54. Varona, R., V. Cadenas, J. Flores, C. Martínez-A, and G. Márquez. 2003. CCR6 has a non-redundant role in the development of inflammatory bowel disease. Eur. J. Immunol. 33:2937-2946. doi:10.1002/eji.200324347
55. Varona, R., V. Cadenas, L. Gómez, C. Martínez-A, and G. Márquez. 2005. CCR6 regulates CD4+ T-cell-mediated acute graft-versus-host disease responses. Blood. 106:18-26. doi:10.1182/blood-2004-08-2996
56. Vieira, P.L., J.R. Christensen, S. Minaee, E.J. O'Neill, F.J. Barrat, A. Boonstra, T. Barthlott, B. Stockinger, D.C. Wraith, and A. O'Garra. 2004. IL-10-secreting regulatory T cells do not express Foxp3 but have comparable regulatory function to naturally occurring CD4+CD25+ regulatory T cells. J. Immunol. 172:5986-5993.
57. Waithman, J., T. Gebhardt, G.M. Davey, W.R. Heath, and F.R. Carbone. 2008. Cutting edge: enhanced IL-2 signaling can convert self-specific T cell response from tolerance to autoimmunity. J. Immunol. 180:5789-5793.
58. Walker, M.R., D.J. Kasprowicz, V.H. Gersuk, A. Benard, M. Van Landeghen, J.H. Buckner, and S.F. Ziegler. 2003. Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells. J. Clin. Invest. 112:1437-1443.