TNF type 2 receptor (p75) lowers the threshold of T cell activation.
T cell activation requires a threshold amount of TCR-mediated signals, an amount that is reduced by signals mediated through costimulatory molecules expressed on the T cell surface. Here the role of TNFR2 (p75) as a putative costimulatory receptor for T cell activation was examined. It was found that p75 deficiency in CD8(+) T cells increased the requirements for TCR agonist approximately 5-fold. Furthermore, p75(-/-) T cells display a marked reduction in the proliferative response to TCR agonist. This hypoproliferative response was associated with delayed kinetics of induction of the acute activation markers CD25 and CD69 as well as a marked decrease in the production of IL-2 and IFN-gamma. The net result is that very few cells are recruited into the dividing population. Interestingly, CD28 costimulation was only partially effective in rescuing the proliferative defect of p75(-/-)CD8(+) T cells. Thus, p75 provides an important costimulatory signal in addition to that provided by CD28 toward optimal T cell proliferation.
Kim
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Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
Teh
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D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D018106:CD28 Antigens / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018448:Models, Immunological; D012333:RNA, Messenger / Q000096:biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology*; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D007376:Interleukin-2; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma