Mature T cells of autoimmune lpr/lpr mice have a defect in antigen-stimulated suicide.
Antigen receptor-stimulated cell death of developing, immature T cells plays an important role in shaping the repertoire of antigens to which mature T cells will respond, but a role for receptor-stimulated death in controlling responses of mature T cells is controversial. Mutant lpr/lpr mice exhibit an autoimmune syndrome similar to systemic lupus erythematosus. Here we demonstrate that these mice have a defect in antigen-stimulated suicide of activated T cells in mature CD4+ and CD8+ T cell compartments. The defective suicide pathway is evident when the T cells are stimulated with antigen on antigen-presenting cells or with immobilized anti-CD3 in the absence of antigen-presenting cells. These studies, in concert with the work of others, suggest that antigen-stimulated death of mature cells may be important both in establishing peripheral tolerance and in limiting inflammation during normal immune responses.
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110.
J H
JH
Russell
B
B
Rush
C
C
Weaver
R
R
Wang
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D016923:Cell Death; D016207:Cytokines / Q000096:biosynthesis; D004768:Enterotoxins / Q000276:immunology; D008213:Lymphocyte Activation; D008232:Lymphoproliferative Disorders / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000941:Antigens; D016207:Cytokines; D004768:Enterotoxins; C026066:enterotoxin A, Staphylococcal