Role of GITR in activation response of T lymphocytes.
In this study, we describe the generation and characterization of mice in which GITR gene (TNFRSF18 [tumor necrosis factor receptor superfamily 18]), a member of the TNFRSF expressed mainly on T lymphocytes, has been ablated (GITR(-/-) mice). Results indicate that GITR inactivation does not impair the normal development of the lymphoid organs but modulates T-cell activation. In fact, when GITR(-/-) T lymphocytes are activated by treatment with an anti-CD3 monoclonal antibody they proliferate more than wild-type cells. Moreover, activated GITR(-/-) T lymphocytes express higher levels of interleukin-2 receptor, produce larger amounts of interleukin-2, and are more sensitive to activation-induced cell death than controls. These results suggest that GITR is involved in the regulation of T-cell receptor/CD3-driven T-cell activation and programmed cell death.
Ronchetti
Simona
S
Department of Clinical and Experimental Medicine, Section of Pharmacology, Perugia University Medical School, Italy.
Nocentini
Giuseppe
G
Riccardi
Carlo
C
Pandolfi
Pier Paolo
PP
D000276:Adjuvants, Immunologic / Q000235:genetics / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D017252:CD3 Complex / Q000502:physiology; D053450:Glucocorticoid-Induced TNFR-Related Protein; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
D000276:Adjuvants, Immunologic; D017252:CD3 Complex; D053450:Glucocorticoid-Induced TNFR-Related Protein; D011948:Receptors, Antigen, T-Cell; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C106544:Tnfrsf18 protein, mouse