Cutting edge: Rac GTPases sensitize activated T cells to die via Fas.
J Immunol
; 179(10): 6384-8, 2007 Nov 15.
Article
en En
| MEDLINE
| ID: mdl-17982024
ABSTRACT
In activated CD4(+) T cells, TCR restimulation triggers apoptosis that depends on interactions between the death receptor Fas and its ligand, FasL. This process, termed restimulation-induced cell death (RICD), is a mechanism of peripheral immune tolerance. TCR signaling sensitizes activated T cells to Fas-mediated apoptosis, but what pathways mediate this process are not known. In this study we identify the Rho GTPases Rac1 and Rac2 as essential components in restimulation-induced cell death. RNA interference-mediated knockdown of Rac GTPases greatly reduced Fas-dependent, TCR-induced apoptosis. The ability of Rac1 to sensitize T cells to Fas-induced apoptosis correlated with Rac-mediated cytoskeletal reorganization, dephosphorylation of the ERM (ezrin/radixin/moesin) family of cytoskeletal linker proteins, and the translocation of Fas to lipid raft microdomains. In primary activated CD4(+) T cells, Rac1 and Rac2 were independently required for maximal TCR-induced apoptosis. Activating Rac signaling may be a novel way to sensitize chronically stimulated lymphocytes to Fas-induced apoptosis, an important goal in the treatment of autoimmune diseases.
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Base de datos:
MEDLINE
Asunto principal:
Activación de Linfocitos
/
Linfocitos T CD4-Positivos
/
Apoptosis
/
Receptor fas
/
Proteínas de Unión al GTP rac
/
Proteína de Unión al GTP rac1
/
Tolerancia Inmunológica
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Immunol
Año:
2007
Tipo del documento:
Article