Suppression of antibody production by TNF-related apoptosis-inducing ligand (TRAIL).
TNF-related apoptosis-inducing ligand (TRAIL), a type II membrane protein belonging to the TNF family, induces apoptotic cell death in various types of tumor cells. However, little is known about its pathological and physiological functions in the immune system. In this study, we showed that administration of neutralizing anti-TRAIL mAb markedly increased serum auto-Ab levels, particularly of IgG1 subclass, in autoimmune-prone C3H/HeJ gld/gld mice without affecting lymphocytosis and lymphocytes populations. In an experimental system where TNP-specific Ab production was induced by immunization with TNP-modified syngeneic B lymphoma cells, expression of TRAIL on these cells significantly reduced TNP-specific Ab production, especially of IgG1 subclass, without affecting T cell priming. These results suggest a new role for TRAIL in the suppression of Ab production.
Kayagaki
Nobuhiko
N
Department of Immunology, Juntendo University School of Medicine, Tokyo 113-8421, Japan. kayagaki@gene.com
Yamaguchi
Noriko
N
Abe
Masaaki
M
Hirose
Sachiko
S
Shirai
Toshikazu
T
Okumura
Ko
K
Yagita
Hideo
H
D000818:Animals; D000906:Antibodies / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology*; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D053222:Fas Ligand Protein; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007274:Injections, Intraperitoneal; D016393:Lymphoma, B-Cell / Q000276:immunology; D008562:Membrane Glycoproteins / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D009154:Mutation; D010851:Picrates; D013601:T-Lymphocytes / Q000276:immunology; D053221:TNF-Related Apoptosis-Inducing Ligand; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D051017:Apoptosis Regulatory Proteins; D001323:Autoantibodies; D015704:CD4 Antigens; D016827:CD8 Antigens; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D010851:Picrates; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C005858:picric acid