title: Potential role for IL-7 in Fas-mediated T cell apoptosis during HIV infection.
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.
authors.affiliation: Department of Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Caroline
authors.initials: C
authors.lastname: Fluur
authors.forename: Angelo
authors.initials: A
authors.lastname: De Milito
authors.forename: Terry J
authors.initials: TJ
authors.lastname: Fry
authors.forename: Nancy
authors.initials: N
authors.lastname: Vivar
authors.forename: Liv
authors.initials: L
authors.lastname: Eidsmo
authors.forename: Ann
authors.initials: A
authors.lastname: Atlas
authors.forename: Cristina
authors.initials: C
authors.lastname: Federici
authors.forename: Paola
authors.initials: P
authors.lastname: Matarrese
authors.forename: Mariantonia
authors.initials: M
authors.lastname: Logozzi
authors.forename: Eva
authors.initials: E
authors.lastname: Rajnavölgyi
authors.forename: Crystal L
authors.initials: CL
authors.lastname: Mackall
authors.forename: Stefano
authors.initials: S
authors.lastname: Fais
authors.forename: Francesca
authors.initials: F
authors.lastname: Chiodi
authors.forename: Bence
authors.initials: B
authors.lastname: Rethi
mesh_terms: D000818:Animals; D017209:Apoptosis; D016764:Cell Polarity; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D007156:Immunologic Memory; D015851:Interleukin-7 / Q000097:blood / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008252:Macaca fascicularis; D020395:Receptors, Interleukin-7 / Q000032:analysis; D013601:T-Lymphocytes / Q000502:physiology*; D019014:fas Receptor / Q000502:physiology*
chemical_list: D015851:Interleukin-7; D020395:Receptors, Interleukin-7; D019014:fas Receptor