Recovery from experimental allergic encephalomyelitis is TGF-β dependent and associated with increases in CD4+LAP+ and CD4+CD25+ T cells

SJL mice are highly susceptible to proteolipid protein (PLP) 139–151-induced experimental allergic encephalomyelitis (EAE). The disease is characterized by a relapsing–remitting type of paralysis. However, the mechanism by which animals recover from EAE is poorly understood. Here, we investigated the role of regulatory T cells in the recovery from disease. We found that Forkhead box P3-expressing CD4 1 CD25 1 T cells were increased in the blood, draining lymph node and spleen of EAE-recovered SJL mice. These cells were anergic and inhibited proliferation of CD4 1 CD25 � T cells to PLP 139–151 or anti-CD3 antibody stimulation. Depletion of CD4 1 CD25 1 T cells during the recovery phase exacerbated disease, resulted in the expansion of IA s /PLP 139–151-tetramer-positive cells and enhanced IFN-c production. In addition, transforming growth factor-b (TGF-b) was shown to be involved in the recovery from EAE as the percentage of CD4 1 cells expressing TGF-b latencyassociated peptide (LAP) on the cell surface increased significantly in blood and spleen of EAErecovered mice as compared with the naive mice and in vivo neutralization of TGF-b abolished recovery from disease. Taken together, our results demonstrate that both CD4 1 CD25 1 and CD4 1 LAP 1 regulatory T cells mediate recovery from PLP 139–151-induced EAE in SJL mice in which TGF-b plays an important role.