CD45 ligation induces programmed cell death in T and B lymphocytes.
Studies have shown an essential role for the CD45 protein tyrosine phosphatase in regulating Ag receptor-derived signals in lymphocytes. Co-ligating CD45 with the Ag receptor, however, can also inhibit receptor signaling, as manifest in T cells by the lack of IL-2 production and proliferation. We report that CD45 ligation alone induces apoptosis in normal T cells, and that death was greatly potentiated by cross-linking CD3. Normal B cells and T and B cell lines were also induced to die with insoluble CD45 mAb. CD45-induced cell death was blocked by inhibitors of protein tyrosine kinases and protein tyrosine phosphatases, but not by inhibitors of RNA or protein synthesis or by cyclosporin A. Morphologically, CD45-mediated apoptosis resembled death induced via CD95 (Fas), as evidenced by nuclear condensation and membrane blebbing, but did not cause DNA fragmentation into oligonucleosomes. Co-ligating CD45 and CD95 either enhanced or inhibited CD45-induced cell death, depending on the degree of CD45 and CD95 cross-linking. Finally, CD45 cross-linking induced its rapid association with the detergent-insoluble cell fraction, suggesting that it becomes linked to the cytoskeleton during CD45-induced apoptosis. These data show a novel role for CD45 in regulating lymphocyte death as well as proliferation.
Klaus
S J
SJ
Department of Immunology, Regional Primate Research Center, University of Washington, Seattle 98195, USA.
Sidorenko
S P
SP
Clark
E A
EA
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000378:metabolism* / Q000494:pharmacology*; D000918:Antibody Specificity; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D002460:Cell Line; D004357:Drug Synergism; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology*; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects; D016399:Lymphoma, T-Cell / Q000276:immunology; D051379:Mice; D011092:Polyethylene Glycols; D012995:Solubility; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D006131:Growth Inhibitors; D007075:Immunoglobulin M; D008024:Ligands; C044203:anti-IgM; D019014:fas Receptor; C024062:nonidet; D011092:Polyethylene Glycols; D017493:Leukocyte Common Antigens