%0 Journal Article
%A Bosque, Alberto
%A Aguiló, Juan Ignacio
%A Alava, M. Angeles
%A Naval, Javier
%A Anel, Alberto
%A Paz Artal, Estela Natividad
%A Allende Martínez, Luis Miguel
%T The induction of Bim expression in human T-cell blasts is dependent on nonapoptotic Fas/CD95 signaling
%D 2006
%@ 0006-4971
%@ 1528-0020
%U https://hdl.handle.net/20.500.14352/98440
%X The BH3-only protein Bim is required for maintaining the homeostasis of the immune system, since Bim regulates the down-modulation of T-cell responses, mainly through cytokine deprivation. Using T-cell blasts from healthy donors and also from patients with autoimmune lymphoproliferative syndromes (ALPSs) due to homozygous loss-of-function mutation of FasL (ALPS-Ic) or heterozygous mutation in the Fas/CD95 death domain (ALPS-Ia), it is shown that the induction of Bim expression during the process of human T-cell blast generation is strictly dependent on FasL/Fas-mediated signaling. The main pathway by which Fas signaling regulates the levels of Bim expression in human T-cell blasts is the death-domain- and caspase-independent generation of discrete levels of H2O2, which results in the net increase of Foxo3a levels. The present results connect the 2 main pathways described until the moment for the control of T-cell responses: death receptor-mediated activation-induced cell death and apoptosis by cytokine deprivation.
%~