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Blood, 15 February 2007, Vol. 109, No. 4, pp. 1627-1635. Prepublished online as a Blood First Edition Paper on October 24, 2006; DOI 10.1182/blood-2006-05-022319. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-05-022319v1 109/4/1627    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bosque, A. Articles by Anel, A. Search for Related Content PubMed PubMed Citation Articles by Bosque, A. Articles by Anel, A. Related Collections Immunobiology Apoptosis Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY The induction of Bim expression in human T-cell blasts is dependent on nonapoptotic Fas/CD95 signaling Alberto Bosque1, Juan Ignacio Aguiló1, M. Angeles Alava1, Estela Paz-Artal2, Javier Naval1, Luis M. Allende2, and Alberto Anel1 1 Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Spain; 2 Servicio de Inmunología, Hospital 12 de Octubre, Madrid, Spain 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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