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, Francesca Chiodi

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Abstract

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 subop-timally 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.

Original languageEnglish
Pages (from-to)1195-1204
Number of pages10
JournalBlood
Volume112
Issue number4
DOIs
Publication statusPublished - Aug 15 2008

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Rethi, B., Vivar, N., Sammicheli, S., Fluur, C., Ruffin, N., Atlas, A., Rajnavolgyi, E., & Chiodi, F. (2008). Priming of T cells to Fas-mediated proliferative signals by interleukin-7. Blood, 112(4), 1195-1204. https://doi.org/10.1182/blood-2007-12-126698