Potential role for IL-7 in Fas-mediated T cell apoptosis during HIV infection |
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Authors: | Fluur Caroline De Milito Angelo Fry Terry J Vivar Nancy Eidsmo Liv Atlas Ann Federici Cristina Matarrese Paola Logozzi Mariantonia Rajnavölgyi Eva Mackall Crystal L Fais Stefano Chiodi Francesca Rethi Bence |
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Affiliation: | Department of Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden. |
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Abstract: | IL-7 promotes survival of resting T lymphocytes and induces T cell proliferation in lymphopenic conditions. As elevated IL-7 levels occur in HIV-infected individuals in addition to high Fas expression on T cells and increased sensitivity to Fas-induced apoptosis, we analyzed whether IL-7 has a regulatory role in Fas-mediated T cell apoptosis. We show that IL-7 up-regulates Fas expression on naive and memory T cells through a mechanism that involves translocation of Fas molecules from intracellular compartments to the cell membrane. IL-7 induced the association of Fas with the cytoskeletal component ezrin and a polarized Fas expression on the cell surface. The potential role of IL-7 in Fas up-regulation in vivo was verified in IL-7-treated macaques and in HIV-infected or chemotherapy treated patients by the correlation between serum IL-7 levels and Fas expression on T cells. IL-7 treatment primed T cells for Fas-induced apoptosis in vitro and serum IL-7 levels correlated with the sensitivity of T cells to Fas-induced apoptosis in HIV-infected individuals. Our data suggest an important role for IL-7 in Fas-mediated regulation of T cell homeostasis. Elevated IL-7 levels associated with lymphopenic conditions, including HIV-infection, might participate in the increased sensitivity of T cells for activation-induced apoptosis. |
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