Priming of T cells to Fas-mediated proliferative signals by interleukin-7.
T-cell depletion associated with HIV infection or cytoreductive therapies triggers potential T-cell regenerative mechanisms such as peripheral T-lymphocyte expansion to weak antigenic stimuli and the increased availability of interleukin-7 (IL-7), a cytokine with potent antiapoptotic and proliferative activities. Deleterious mechanisms also associated with lymphopenia, such as increased Fas expression and apoptosis of T cell, however, may result in opposing effects. In this study, we show that Fas molecules, primarily associated with T-cell depletion in lymphopenic settings, may also contribute to compensatory T-cell expansion through transmitting costimulatory signals to suboptimally activated T cells. Proliferation of T lymphocytes in response to concomitant Fas and T-cell receptor (TCR) triggering was shown to be increased in HIV-infected individuals compared with noninfected controls. As IL-7 levels are often elevated in lymphopenic individuals in association with increased Fas expression, we analyzed whether IL-7 would influence Fas-mediated proliferative signals in T cells. We show that IL-7 is able to increase the efficacy of Fas to induce proliferation of suboptimally activated T cells. Thus, high IL-7 levels associated with lymphopenic conditions may simultaneously induce sensitivity to Fas-mediated apoptosis in nonactivated T cells and increase Fas-induced costimulatory signals in T cells recognizing low-affinity antigens.
Rethi
Bence
B
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Vivar
Nancy
N
Sammicheli
Stefano
S
Fluur
Caroline
C
Ruffin
Nicolas
N
Atlas
Ann
A
Rajnavolgyi
Eva
E
Chiodi
Francesca
F
D017951:Antigen Presentation; D017209:Apoptosis; D016022:Case-Control Studies; D049109:Cell Proliferation; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology*; D008231:Lymphopenia / Q000276:immunology; D008297:Male; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D019014:fas Receptor / Q000378:metabolism*
D015851:Interleukin-7; D019014:fas Receptor