Interplay between pathogenic Th17 and regulatory T cells.
Autoimmune diseases arise from a break in tolerance toward self-antigens and are characterised by the development of pathogenic T cell populations infiltrating the target organ. Regulatory T cells play an important role in maintaining self-tolerance through their inhibitory functions on effector T cells. The usage of ex vivo-generated regulatory T cells (Treg) has been regarded as a potentially attractive therapeutic approach for autoimmune diseases. However, the dynamics of Treg in autoimmunity are not well understood. Here, we summarise our published findings on the interplay between Treg and Th17 effector cells in vivo during experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. We have developed Foxp3gfp "knock-in" mice and myelin oligodendrocyte glycoprotein (MOG)(35-55)/IA(b) (MHC class II)-tetramers to track autoantigen-specific Treg in vivo during EAE. On immunisation with MOG, Treg cells were detected in the central nervous system (CNS) as early as day 10. However, at the onset of disease, the accumulation of MOG-specific effector T cells (T-eff) largely prevailed. Subsequently, during remission T-eff rapidly contracted whereas a highly suppressive Treg population persisted in the CNS. The interplay between effector Th17 and Treg extend beyond their functions in vivo as we and others have identified the factors responsible for Th17 differentiation. While TGF-beta is a critical differentiation factor for Treg cells, IL6 completely inhibits the generation of Treg cells induced by TGF-beta. Instead, IL6 and TGF-beta together induce the differentiation of pathogenic Th17 cells. Our data demonstrate a dichotomy in the generation of Th17 cells that induce autoimmunity and Treg cells that inhibit autoimmune tissue injury.
Oukka
Mohamed
M
Center for Neurologic Diseases, Brigham and Women's Hospital Harvard Medical School, Boston, MA 02115, USA. moukka@rics.bwh.harvard.edu
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002490:Central Nervous System / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology; D007114:Immunization / Q000379:methods; D051379:Mice; D018448:Models, Immunological; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000276:immunology; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D001324:Autoantigens; D000939:Epitopes; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein