Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation

Nature Medicine

Volumn 13, Issue 4, 2007, Pages 423-431

  Korn, Thomas ^a   Reddy, Jayagopala ^a   Gao, Wenda ^a   Bettelli, Estelle ^a   Awasthi, Amit ^a   Petersen, Troels R ^b   Bäckström, B Thomas ^b   Sobel, Raymond A ^c,d   Wucherpfennig, Kai W ^a   Strom, Terry B ^a   Oukka, Mohamed ^a   Kuchroo, Vijay K ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b MALAGHAN INSTITUTE OF MEDICAL RESEARCH   (New Zealand)

^c VA PALO ALTO HEALTH CARE SYSTEM   (United States)

^d STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AUTOANTIGEN; GREEN FLUORESCENT PROTEIN; INTERLEUKIN 6; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; MYELIN; MYELIN OLIGODENDROCYTE GLYCOPROTEIN; TETRAMER; TRANSCRIPTION FACTOR FOXP3; TUMOR NECROSIS FACTOR;

ALLERGIC ENCEPHALOMYELITIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; AUTOIMMUNITY; CD4+ T LYMPHOCYTE; CELL COMPARTMENTALIZATION; CELL ISOLATION; CENTRAL NERVOUS SYSTEM; CYTOKINE RELEASE; DISEASE CONTROL; EFFECTOR CELL; IN VIVO STUDY; MOUSE; MULTIPLE SCLEROSIS; NONHUMAN; PERIPHERAL LYMPHOCYTE; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; TARGET ORGAN;

ANIMALS; AUTOIMMUNITY; BRAIN; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; FORKHEAD TRANSCRIPTION FACTORS; GLYCOPROTEINS; GREEN FLUORESCENT PROTEINS; IMMUNOHISTOCHEMISTRY; IMMUNOTHERAPY; MICE; MODELS, IMMUNOLOGICAL; MULTIPLE SCLEROSIS; PEPTIDE FRAGMENTS; T-LYMPHOCYTES, REGULATORY;

ANIMALIA; MUS;

EID: 34147128572     PISSN: 10788956     EISSN: 1546170X     Source Type: Journal    
DOI: 10.1038/nm1564     Document Type: Article

References (47)

1. + regulatory T cells in immunological tolerance to self and non-self. Nat. Immunol. 6, 345-352 (2005).
2. Kim, J.M., Rasmussen, J.P. & Rudensky, A.Y. Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat. Immunol. 8, 191-197 (2007).
3. + regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. USA 101, 15434-15439 (2004).
4. + regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis. J. Immunol. 169, 4712-4716 (2002).
5. + T regulatory cells dependent on ICOS promote regulation of effector cells in the prediabetic lesion. J. Exp. Med. 199, 1479-1489 (2004).
6. + regulatory T lymphocytes in neonatal NOD mice. Ann. NY Acad. Sci. 1051, 72-87 (2005).
7. + cell depletion hastens the onset of severe disease in collagen-induced arthritis. Arthritis Rheum. 48, 1452-1460 (2003).
8. + regulatory T cells in patients with multiple sclerosis. J. Exp. Med. 199, 971-979 (2004).
9. +CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis. Eur. J. Immunol. 35, 3343-3352 (2005).
10. Crispin, J.C., Martinez, A. & Alcocer-Varela, J. Quantification of regulatory T cells in patients with systemic lupus erythematosus. J. Autoimmun. 21, 273-276 (2003).
11. Alvarado-Sanchez, B. et al. Regulatory T cells in patients with systemic lupus erythematosus. J. Autoimmun. 27, 110-118 (2006).
12. + immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J. Exp. Med. 188, 287-296 (1998).
13. + regulatory T cells in vivo. J. Exp. Med. 198, 249-258 (2003).
14. Klein, L., Khazaie, K. & von Boehmer, H. In vivo dynamics of antigen-specific regulatory T cells not predicted from behavior in vitro. Proc. Natl. Acad. Sci. USA 100, 8886-8891 (2003).
15. Hsieh, C.S., Zheng, Y., Liang, Y., Fontenot, J.D. & Rudensky, A.Y. An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoires. Nat. Immunol. 7, 401-410 (2006).
16. + T cells, expanded with dendritic cells presenting a single autoantigenic peptide, suppress autoimmune diabetes. J. Exp. Med. 199, 1467-1477 (2004).
17. Veldhoen, M., Hocking, R.J., Atkins, C.J., Locksley, R.M. & Stockinger, B. TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24, 179-189 (2006).
18. H17 lineage. Nature 441, 231-234 (2006).
19. H17 and regulatory T cells. Nature 441, 235-238 (2006).
20. + regulatory cells within the central nervous system. J. Immunol. 175, 3025-3032 (2005).
21. Marson, A. et al. Foxp3 occupancy and regulation of key target genes during T-cell stimulation. Nature 445, 931-935 (2007).
22. Gavin, M.A. et al. Foxp3-dependent programme of regulatory T-cell differentiation. Nature 445, 771-775 (2007).
23. Zheng, Y. et al. Genome-wide analysis of Foxp3 target genes in developing and mature regulatory T cells. Nature 445, 936-940 (2007).
24. Fontenot, J.D. et al. Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 22, 329-341 (2005).
25. Bluestone, J.A. & Abbas, A.K. Natural versus adaptive regulatory T cells. Nat. Rev. Immunol. 3, 253-257 (2003).
26. + suppressor T cells in vivo. Nat. Immunol. 3, 33-41 (2002).
27. Bettelli, E. et al. Myelin oligodendrocyte glycoprotein-specific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritis. J. Exp. Med. 197, 1073-1081 (2003).
28. Bagaeva, L.V., Williams, L.P. & Segal, B.M. IL-12 dependent/IFNγ independent expression of CCR5 by myelin-reactive T cells correlates with encephalitogenicity. J. Neuroimmunol. 137, 109-116 (2003).
29. Glabinski, A.R., Bielecki, B., O'Bryant, S., Selmaj, K. & Ransohoff, R.M. Experimental autoimmune encephalomyelitis: CC chemokine receptor expression by trafficking cells. J. Autoimmun. 19, 175-181 (2002).
30. + regulatory T cells. J. Exp. Med. 199, 303-313 (2004).
31. Apostolou, I. & von Boehmer, H. In vivo instruction of suppressor commitment in naive T cells. J. Exp. Med. 199, 1401-1408 (2004).
32. Liu, Y., Teige, I., Birnir, B. & Issazadeh-Navikas, S. Neuron-mediated generation of regulatory T cells from encephalitogenic T cells suppresses EAE. Nat. Med. 12, 518-525 (2006).
33. + Treg development and function during allergic airway inflammation in vivo. J. Clin. Invest. 115, 313-325 (2005).
34. H17 cells in relapsing EAE. Nat. Immunol. 8, 172-180 (2007).
35. Gijbels, K., Brocke, S., Abrams, J.S. & Steinman, L. Administration of neutralizing antibodies to interleukin-6 (IL-6) reduces experimental autoimmune encephalomyelitis and is associated with elevated levels of IL-6 bioactivity in central nervous system and circulation. Mol. Med. 1, 795-805 (1995).
36. Di Marco, R. et al. Curative effects of recombinant human Interleukin-6 in DA rats with protracted relapsing experimental allergic encephalomyelitis. J. Neuroimmunol. 116, 168-177 (2001).
37. Greter, M. et al. Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis. Nat. Med. 11, 328-334 (2005).
38. McMahon, E.J., Bailey, S.L., Castenada, C.V., Waldner, H. & Miller, S.D. Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis. Nat. Med. 11, 335-339 (2005).
39. Tanchot, C., Vasseur, F., Pontoux, C., Garcia, C. & Sarukhan, A. Immune regulation by self-reactive T cells is antigen specific. J. Immunol. 172, 4285-4291 (2004).
40. + regulatory T cells in anti-myelin basic protein T cell receptor transgenic mice. Proc. Natl. Acad. Sci. USA 99, 8213-8218 (2002).
41. + T cell-mediated suppression by dendritic cells. Science 299, 1033-1036 (2003).
42. Langrish, C.L. et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J. Exp. Med. 201, 233-240 (2005).
43. Kolls, J.K. & Linden, A. Interleukin-17 family members and inflammation. Immunity 21, 467-476 (2004).
44. + regulatory T cells in rheumatoid arthritis: differences in the presence, phenotype, and function between peripheral blood and synovial fluid. Arthritis Rheum. 50, 2775-2785 (2004).
45. + T cells in rheumatic joints. Scand. J. Immunol. 63, 444-452 (2006).
46. + regulatory T cells in inflamed synovia. J. Exp. Med. 201, 1793-1803 (2005).
47. Ehrenstein, M.R. et al. Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFalpha therapy. J. Exp. Med. 200, 277-285 (2004).