TNF/TNFR family members in costimulation of T cell responses.
Several members of the tumor necrosis factor receptor (TNFR) family function after initial T cell activation to sustain T cell responses. This review focuses on CD27, 4-1BB (CD137), OX40 (CD134), HVEM, CD30, and GITR, all of which can have costimulatory effects on T cells. The effects of these costimulatory TNFR family members can often be functionally, temporally, or spatially segregated from those of CD28 and from each other. The sequential and transient regulation of T cell activation/survival signals by different costimulators may function to allow longevity of the response while maintaining tight control of T cell survival. Depending on the disease condition, stimulation via costimulatory TNF family members can exacerbate or ameliorate disease. Despite these complexities, stimulation or blockade of TNFR family costimulators shows promise for several therapeutic applications, including cancer, infectious disease, transplantation, and autoimmunity.
Watts
Tania H
TH
Department of Immunology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada. tania.watts@utoronto.ca
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D053282:CD27 Ligand; D053450:Glucocorticoid-Induced TNFR-Related Protein; D006801:Humans; D017730:Ki-1 Antigen / Q000276:immunology; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D017475:Receptors, Nerve Growth Factor / Q000276:immunology; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D015703:Antigens, CD; D053282:CD27 Ligand; C505771:CD70 protein, human; C505772:Cd70 protein, mouse; D053450:Glucocorticoid-Induced TNFR-Related Protein; D017730:Ki-1 Antigen; D008565:Membrane Proteins; D017475:Receptors, Nerve Growth Factor; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus; C506028:TNFRSF14 protein, human; C505716:TNFRSF4 protein, human; C505714:TNFRSF9 protein, human; C506029:Tnfrsf14 protein, mouse; C106544:Tnfrsf18 protein, mouse; C505717:Tnfrsf4 protein, mouse; C505715:Tnfrsf9 protein, mouse; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha