1. IL-7 promotes CD95-induced apoptosis in B cells via the IFN-γ/STAT1 pathway
- Author
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Bence Rethi, Thang Pham Hong, Stefano Sammicheli, Francesca Chiodi, Nicolas Ruffin, Nancy Vivar, Rebecka Lantto, and Linh Dang Vu Phuong
- Subjects
B Cells ,T-Lymphocytes ,Priming (immunology) ,lcsh:Medicine ,Apoptosis ,Interleukin 21 ,Molecular Cell Biology ,Cytotoxic T cell ,IL-2 receptor ,lcsh:Science ,Immune Response ,B-Lymphocytes ,Multidisciplinary ,Cell Death ,T Cells ,Fas receptor ,Cell biology ,Up-Regulation ,medicine.anatomical_structure ,STAT1 Transcription Factor ,Cytokines ,Medicine ,Infectious diseases ,HIV clinical manifestations ,Research Article ,Interleukin Receptor Common gamma Subunit ,Signal Transduction ,T cell ,Immune Cells ,Naive B cell ,Immunology ,Immunopathology ,Viral diseases ,Biology ,Immune Activation ,Immunomodulation ,Immune Deficiency ,Interferon-gamma ,medicine ,Humans ,fas Receptor ,B cell ,Interleukin-7 ,lcsh:R ,Immunity ,Immunoregulation ,HIV ,Molecular biology ,Solubility ,Immune System ,lcsh:Q ,Stromal Cells - Abstract
Interleukin-7 (IL-7) concentrations are increased in the blood of CD4+ T cell depleted individuals, including HIV-1 infected patients. High IL-7 levels might stimulate T cell activation and, as we have shown earlier, IL-7 can prime resting T cell to CD95 induced apoptosis as well. HIV-1 infection leads to B cell abnormalities including increased apoptosis via the CD95 (Fas) death receptor pathway and loss of memory B cells. Peripheral B cells are not sensitive for IL-7, due to the lack of IL-7Ra expression on their surface; however, here we demonstrate that high IL-7 concentration can prime resting B cells to CD95-mediated apoptosis via an indirect mechanism. T cells cultured with IL-7 induced high CD95 expression on resting B cells together with an increased sensitivity to CD95 mediated apoptosis. As the mediator molecule responsible for B cell priming to CD95 mediated apoptosis we identified the cytokine IFN-γ that T cells secreted in high amounts in response to IL-7. These results suggest that the lymphopenia induced cytokine IL-7 can contribute to the increased B cell apoptosis observed in HIV-1 infected individuals.
- Published
- 2011