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

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

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607 Scopus citations

Abstract

Treatment with ex vivo-generated regulatory T cells (T-reg) has been regarded as a potentially attractive therapeutic approach for autoimmune diseases. However, the dynamics and function of T-reg in autoimmunity are not well understood. Thus, we developed Foxp3gfp knock-in (Foxp3gfp.KI) mice and myelin oligodendrocyte glycoprotein (MOG)35-55/IAb (MHC class II) tetramers to track autoantigen-specific effector T cells (T-eff) and T-reg in vivo during experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. MOG tetramer-reactive, Foxp3+ T-reg expanded in the peripheral lymphoid compartment and readily accumulated in the central nervous system (CNS), but did not prevent the onset of disease. Foxp3+ T cells isolated from the CNS were effective in suppressing naive MOG-specific T cells, but failed to control CNS-derived encephalitogenic T-eff that secreted interleukin (IL)-6 and tumor necrosis factor (TNF). Our data suggest that in order for CD4+Foxp3+ T-reg to effectively control autoimmune reactions in the target organ, it may also be necessary to control tissue inflammation.

Original languageEnglish (US)
Pages (from-to)423-431
Number of pages9
JournalNature Medicine
Volume13
Issue number4
DOIs
StatePublished - Apr 2007

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Korn, T., Reddy, J., Gao, W., Bettelli, E., Awasthi, A., Petersen, T. R., Bäckström, B. T., Sobel, R. A., Wucherpfennig, K. W., Strom, T. B., Oukka, M., & Kuchroo, V. K. (2007). Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation. Nature Medicine, 13(4), 423-431. https://doi.org/10.1038/nm1564