Glucocorticoid-induced TNF receptor functions as a costimulatory receptor that promotes survival in early phases of T cell activation.
Glucocorticoid-induced TNFR (GITR) is a member of the TNFR family that can inhibit the suppressive function of regulatory T cells and promote the survival and activation of T cells. However, little is known about the molecular mechanisms regulating T cell survival and activation downstream of GITR. To gain further insight into the cellular events and signaling pathways triggered by GITR, survival, proliferation, and cytokine production as well as activation of MAPKs and NF-kappaB were monitored after cross-linking of the receptor on naive and activated T cells. GITR cross-linking provided costimulation of naive and activated T cells and resulted in activation of MAPKs and NF-kappaB. Although GITR-induced signaling pathways augmented the survival of naive T cells, they were not sufficient to inhibit activation-induced cell death triggered by CD3 cross-linking of activated T cells. Differences in the contributions of GITR to cell survival between naive and activated T cells suggest that the receptor triggers specific pathways depending on the activation state of the T cell.
Esparza
Edward M
EM
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Arch
Robert H
RH
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D016923:Cell Death / Q000276:immunology; D049109:Cell Proliferation; D002470:Cell Survival / Q000276:immunology; D053450:Glucocorticoid-Induced TNFR-Related Protein; D007376:Interleukin-2 / Q000096:biosynthesis; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism / Q000502:physiology*; D016192:Resting Phase, Cell Cycle / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D048069:Tumor Necrosis Factors
D002352:Carrier Proteins; D053450:Glucocorticoid-Induced TNFR-Related Protein; D007376:Interleukin-2; D008024:Ligands; D016328:NF-kappa B; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C106544:Tnfrsf18 protein, mouse; C478966:Tnfsf18 protein, mouse; D048069:Tumor Necrosis Factors; D020928:Mitogen-Activated Protein Kinases