Abstract
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 Valpha, but not Vbeta, 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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Autoimmune Diseases / genetics
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Autoimmune Diseases / immunology*
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CD40 Antigens / genetics
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CD40 Antigens / physiology*
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Clone Cells
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Cloning, Molecular
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DNA, Complementary / isolation & purification
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DNA-Binding Proteins / biosynthesis*
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DNA-Binding Proteins / genetics*
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Diabetes Mellitus, Type 1 / genetics
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Diabetes Mellitus, Type 1 / immunology
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Female
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Gene Expression Regulation / immunology*
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Genes, RAG-1 / immunology*
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Genes, T-Cell Receptor alpha / genetics
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Genes, T-Cell Receptor beta / genetics
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Mice
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Mice, Inbred NOD
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RNA, Messenger / biosynthesis
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RNA, Messenger / isolation & purification
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Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Signal Transduction / genetics
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Signal Transduction / immunology
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Spleen / cytology
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Spleen / immunology
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Spleen / metabolism
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T-Lymphocyte Subsets / cytology*
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
Substances
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CD40 Antigens
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DNA, Complementary
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DNA-Binding Proteins
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RNA, Messenger
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Rag2 protein, mouse
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Receptors, Antigen, T-Cell, alpha-beta
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V(D)J recombination activating protein 2