Cutting edge: CD40-induced expression of recombination activating gene (RAG) 1 and RAG2: a mechanism for the generation of autoaggressive T cells in the periphery.
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.
Vaitaitis
Gisela M
GM
Department of Medicine and Webb-Waring Institute for Cancer, Aging and Antioxidant Research, University of Colorado, Denver, CO 80262, USA.
Poulin
Michelle
M
Sanderson
Richard J
RJ
Haskins
Kathryn
K
Wagner
David H
DH
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D019013:CD40 Antigens / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002999:Clone Cells; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D016654:Genes, RAG-1 / Q000276:immunology*; D019673:Genes, T-Cell Receptor alpha / Q000235:genetics; D019674:Genes, T-Cell Receptor beta / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D019013:CD40 Antigens; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C499308:Rag2 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; C064655:V(D)J recombination activating protein 2