Submitted December 4, 2007
Accepted April 8, 2008
Priming of T cells to Fas-mediated proliferative signals by Interleukin-7
Bence Rethi, Nancy Vivar, Stefano Sammicheli, Caroline Fluur, Nicolas Ruffin, Ann Atlas, Eva Rajnavolgyi, and Francesca Chiodi*
Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden
Infectious Diseases Unit, Department of Medicine, Karolinska University Hospital, Solna, Sweden
Institute of Immunology, Medical and Health Science Center, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
* Corresponding author; email: francesca.chiodi{at}ki.se.
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 IL-7, a cytokine with potent anti-apoptotic and proliferative activities. Deleterious mechanisms also associated with lymphopenia, such as increased Fas expression and apoptosis of T cell, may however 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 TCR triggering was shown to be increased in HIV-infected individuals as compared to non-infected 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 non-activated T cells and increase Fas-induced costimulatory signals in T cells recognizing low affinity antigens.
