International Immunology, Vol. 16, No. 2, pp. 249-256,
February 2004
© 2004 Japanese Society for Immunology
IL-10 is involved in the suppression of experimental autoimmune encephalomyelitis by CD25+CD4+ regulatory T cells
1 Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA 2 Department of Immunopathology, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan
Correspondence to: H. L. Weiner; E-mail: hweiner{at}rics.bwh.harvard.edu
Transmitting editor: L. Steinman
CD25+CD4+ regulatory T cells inhibit the activation of autoreactive T cells in vitro and in vivo, and suppress organ-specific autoimmune diseases. The mechanism of CD25+CD4+ T cells in the regulation of experimental autoimmune encephalomyelitis (EAE) is poorly understood. To assess the role of CD25+CD4+ T cells in EAE, SJL mice were immunized with myelin proteolipid protein (PLP)139–151 to develop EAE and were treated with anti-CD25 mAb. Treatment with anti-CD25 antibody following immunization resulted in a significant enhancement of EAE disease severity and mortality. There was increased inflammation in the central nervous system (CNS) of anti-CD25 mAb-treated mice. Anti-CD25 antibody treatment caused a decrease in the percentage of CD25+CD4+ T cells in blood, peripheral lymph node (LN) and spleen associated with increased production of IFN-
and a decrease in IL-10 production by LN cells stimulated with PLP130–151 in vitro. In addition, transfer of CD25+CD4+ regulatory T cells from naive SJL mice decreased the severity of active EAE. In vitro, anti-CD3-stimulated CD25+CD4+ T cells from naive SJL mice secreted IL-10 and IL-10 soluble receptor (sR) partially reversed the in vitro suppressive activity of CD25+CD4+ T cells. CD25+CD4+ T cells from IL-10-deficient mice were unable to suppress active EAE. These findings demonstrate that CD25+CD4+ T cells suppress pathogenic autoreactive T cells in actively induced EAE and suggest they may play an important natural regulatory function in controlling CNS autoimmune disease through a mechanism that involves IL-10.
Keywords: CD25+CD4+ regulatory T cells, experimental autoimmune encephalomyelitis, IL-10
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