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A dual role of IFN-alpha in the balance between proliferation and death of human CD4+ T lymphocytes during primary response.

Abstract : 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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-00193639
Contributor : Marie-Dominique Aytac <>
Submitted on : Tuesday, December 4, 2007 - 11:27:31 AM
Last modification on : Monday, January 13, 2020 - 5:08:10 PM

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Elisabetta Dondi, Gaël Roué, Victor J Yuste, Santos A Susin, Sandra Pellegrini. A dual role of IFN-alpha in the balance between proliferation and death of human CD4+ T lymphocytes during primary response.. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2004, 173 (6), pp.3740-7. ⟨10.4049/jimmunol.173.6.3740⟩. ⟨pasteur-00193639⟩

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