%0 Journal Article %T A dual role of IFN-alpha in the balance between proliferation and death of human CD4+ T lymphocytes during primary response. %+ Signalisation des Cytokines - Cytokine Signaling %+ Apoptose et Système Immunitaire (ASI) %A Dondi, Elisabetta %A Roué, Gaël %A Yuste, Victor J %A Susin, Santos A %A Pellegrini, Sandra %< avec comité de lecture %@ 0022-1767 %J Journal of Immunology %I Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists %V 173 %N 6 %P 3740-7 %8 2004-09-15 %D 2004 %R 10.4049/jimmunol.173.6.3740 %M 15356120 %Z Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biologyJournal articles %X Type I IFNs (IFN-alphabeta) enhance immune responses, notably T cell-mediated responses, in part by promoting the functional activities of dendritic cells. In this study, we analyzed the direct impact of IFN-alpha on proliferative and apoptotic signals upon in vitro activation of human naive CD4+ T lymphocytes. We demonstrate that IFN-alpha protects T cells from the intrinsic mitochondrial-dependent apoptosis early upon TCR/CD28 activation. IFN-alpha acts by delaying entry of cells into the G1 phase of the cell cycle, as well as by increasing Bcl-2 and limiting Bax activation. Later, upon activation, T cells that were exposed to IFN-alpha showed increased levels of surface Fas associated with partially processed caspase-8, a key component of the extrinsic apoptotic pathway. Caspase-8 processing was augmented furthermore by Fas ligation. Overall, these findings support a model whereby IFN-alpha favors an enhanced clonal expansion, yet it sensitizes cells to the Ag-induced cell death occurring at the end of an immune response. These observations point to a complex role of type I IFN in regulating the magnitude of proliferation and survival of naive CD4+ T cells during primary response and underline how crucial could be the timing of exposure to this cytokine. %G English %L pasteur-00193639 %U https://pasteur.hal.science/pasteur-00193639 %~ PASTEUR %~ CNRS %~ RIIP_PARIS