title: TNF receptor-associated factor 3 is required for T cell-mediated immunity and TCR/CD28 signaling.
abstract: We recently reported that TNFR-associated factor (TRAF)3, a ubiquitously expressed adaptor protein, promotes mature B cell apoptosis. However, the specific function of TRAF3 in T cells has remained unclear. In this article, we report the generation and characterization of T cell-specific TRAF3(-/-) mice, in which the traf3 gene was deleted from thymocytes and T cells. Ablation of TRAF3 in the T cell lineage did not affect CD4 or CD8 T cell populations in secondary lymphoid organs or the numbers or proportions of CD4(+),CD8(+) or double-positive or double-negative thymocytes, except that the T cell-specific TRAF3(-/-) mice had a 2-fold increase in FoxP3(+) T cells. In striking contrast to mice lacking TRAF3 in B cells, the T cell TRAF3-deficient mice exhibited defective IgG1 responses to a T-dependent Ag, as well as impaired T cell-mediated immunity to infection with Listeria monocytogenes. Surprisingly, we found that TRAF3 was recruited to the TCR/CD28 signaling complex upon costimulation and that TCR/CD28-mediated proximal and distal signaling events were compromised by TRAF3 deficiency. These findings provide insights into the roles played by TRAF3 in T cell activation and T cell-mediated immunity.
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Xie
authors.forename: Zachary J
authors.initials: ZJ
authors.lastname: Kraus
authors.forename: Laura L
authors.initials: LL
authors.lastname: Stunz
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Gail A
authors.initials: GA
authors.lastname: Bishop
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D018106:CD28 Antigens / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D002478:Cells, Cultured; D007111:Immunity, Cellular / Q000235:genetics; D007074:Immunoglobulin G / Q000096:biosynthesis; D008088:Listeriosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D048008:TNF Receptor-Associated Factor 3 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D000907:Antibodies, Bacterial; D018106:CD28 Antigens; D007074:Immunoglobulin G; D011948:Receptors, Antigen, T-Cell; D048008:TNF Receptor-Associated Factor 3