Potential role for IL-7 in Fas-mediated T cell apoptosis during HIV infection.
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.
Fluur
Caroline
C
Department of Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden.
De Milito
Angelo
A
Fry
Terry J
TJ
Vivar
Nancy
N
Eidsmo
Liv
L
Atlas
Ann
A
Federici
Cristina
C
Matarrese
Paola
P
Logozzi
Mariantonia
M
Rajnavölgyi
Eva
E
Mackall
Crystal L
CL
Fais
Stefano
S
Chiodi
Francesca
F
Rethi
Bence
B
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*
D015851:Interleukin-7; D020395:Receptors, Interleukin-7; D019014:fas Receptor