Surface expression of TRAIL/Apo-2 ligand in activated mouse T and B cells.
Like other members of the TNF family, TRAIL/Apo-2 ligand induces apoptosis in sensitive target cells in a caspase-dependent fashion. We recently found that TRAIL may be constitutively expressed on the surface of mouse and human tumor cells of T and B origin. To define the pattern of TRAIL expression in normal immune cells, freshly isolated splenocytes, Concanavalin A/IL-2-activated T cells and lipopolysaccharide-activated B cells were analyzed by surface staining with or without secondary stimulation. Activated, but not resting, CD3+ cells expressed TRAIL in an activation-dependent fashion. Conversely, freshly isolated B220+ cells displayed surface TRAIL and CD95L that were retained following activation. Restimulation with the protein kinase C activator phorbol 12-myristate 13-acetate and the calcium ionophore ionomycin or an agonistic anti-CD3 monoclonal antibody induced significant up-regulation of surface TRAIL and CD95L in CD3+, TCRalphabeta cells with CD4+ or CD8+ phenotype. Similarly to CD95L, TRAIL up-regulation was protein synthesis dependent and cyclosporin A sensitive. These results indicate that both TRAIL and CD95L are displayed on the cell surface of activated immune cells and may thus represent complementary effector pathways in the regulatory functions of T and B cells.
Mariani
S M
SM
Division of Immunogenetics, German Cancer Research Center, Heidelberg.
Krammer
P H
PH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology; D051017:Apoptosis Regulatory Proteins; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D017252:CD3 Complex / Q000032:analysis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000032:analysis; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D015854:Up-Regulation / Q000276:immunology; D019014:fas Receptor / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D051017:Apoptosis Regulatory Proteins; D017252:CD3 Complex; D008024:Ligands; D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D017493:Leukocyte Common Antigens