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

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.