title: IL-7 promotes CD95-induced apoptosis in B cells via the IFN-γ/STAT1 pathway.
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.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Stefano
authors.initials: S
authors.lastname: Sammicheli
authors.forename: Vu Phuong Linh
authors.initials: VP
authors.lastname: Dang
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ruffin
authors.forename: Hong Thang
authors.initials: HT
authors.lastname: Pham
authors.forename: Rebecka
authors.initials: R
authors.lastname: Lantto
authors.forename: Nancy
authors.initials: N
authors.lastname: Vivar
authors.forename: Francesca
authors.initials: F
authors.lastname: Chiodi
authors.forename: Bence
authors.initials: B
authors.lastname: Rethi
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism*; D053631:Interleukin Receptor Common gamma Subunit / Q000378:metabolism; D015851:Interleukin-7 / Q000494:pharmacology*; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D012995:Solubility / Q000187:drug effects; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D019014:fas Receptor / Q000378:metabolism*
chemical_list: C491901:FAS protein, human; C508605:IL7 protein, human; D053631:Interleukin Receptor Common gamma Subunit; D015851:Interleukin-7; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D019014:fas Receptor; D007371:Interferon-gamma