International Immunology Advance Access originally published online on March 15, 2006
International Immunology 2006 18(4):495-503; doi:10.1093/intimm/dxh390
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Published by Oxford University Press 2006
Recovery from experimental allergic encephalomyelitis is TGF-ß dependent and associated with increases in CD4+LAP+ and CD4+CD25+ T cells
1 Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
2 Present address: 77 Avenue Louis Pasteur, HIM 730, Boston, MA 02115, USA
Correspondence to: H. L. Weiner; E-mail: hweiner{at}rics.bwh.harvard.edu
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+CD25+ 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+CD25– T cells to PLP 139–151 or anti-CD3 antibody stimulation. Depletion of CD4+CD25+ T cells during the recovery phase exacerbated disease, resulted in the expansion of IAs/PLP 139–151-tetramer-positive cells and enhanced IFN-
production. In addition, transforming growth factor-ß (TGF-ß) was shown to be involved in the recovery from EAE as the percentage of CD4+ cells expressing TGF-ß latency-associated peptide (LAP) on the cell surface increased significantly in blood and spleen of EAE-recovered mice as compared with the naive mice and in vivo neutralization of TGF-ß abolished recovery from disease. Taken together, our results demonstrate that both CD4+CD25+ and CD4+LAP+ regulatory T cells mediate recovery from PLP 139–151-induced EAE in SJL mice in which TGF-ß plays an important role.
Keywords: EAE, LAP, regulatory T cells, TGF-ß
Transmitting editor: L. Steinman
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