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CUTTING EDGE |
,
* Department of Medicine and Webb-Waring Institute for Cancer, Aging, and Antioxidant Research,
Department of Immunology, and
Barbara Davis Center for Childhood Diabetes, Health Sciences Center, University of Colorado, Denver, CO 80262
It has been speculated that autoimmune diseases are caused by failure of central tolerance. However, this remains controversial. We have suggested that CD40 expression identifies autoaggressive T cells in the periphery of autoimmune prone mice. In this study, we report that CD40 was cloned from autoaggressive T cells and that engagement induces expression and nuclear translocation of the recombinases, recombination activating gene (RAG) 1 and RAG2 in the autoaggressive, but not in the nonautoaggressive, peripheral T cell population. Furthermore, we demonstrate that CD40 engagement induces altered TCR V
, but not V
, expression in these cells. Therefore, CD40-regulated expression of RAG1 and RAG2 in peripheral T cells may constitute a novel pathway for the generation of autoaggressive T cells.
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