Myelin-specific Regulatory T Cells Accumulate in the CNS but Fail to Control Autoimmune Inflammation

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2007 Mar 27

PMID 17384649

Citations 408

Authors

Thomas Korn

Jayagopala Reddy

Wenda Gao

Estelle Bettelli

Amit Awasthi

Troels R Petersen

B Thomas Backstrom

Raymond A Sobel

Kai W Wucherpfennig

Terry B Strom

Mohamed Oukka

Vijay K Kuchroo

Affiliations

Soon will be listed here.

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)/IA(b) (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.

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