IFN-γ regulates Fas ligand expression in human CD4+ T lymphocytes and controls their anti-mycobacterial cytotoxic functions

Daniela Boselli, Giuliana Losana, Paola Bernabei, Daniela Bosisio, Pamela Drysdale, Rolf Kiessling, John S H Gaston, David Lammas, Jean Laurent Casanova, Dinakantha S. Kumararatne, Francesco Novelli

Research output: Contribution to journalArticle

Abstract

Fas and Fas Ligand (FasL) expression, activation-induced cell death (AICD) and mycobacterial antigen-specific cytotoxicity of peripheral T cells from patients with complete inherited IFN-γ receptor 1 binding chain deficiency (IFN-γR1-/-) were investigated. Fas was equally expressed in both normal and deficient T lymphoblasts and they underwent apoptosis when stimulated with agonist anti-Fas mAb. By contrast, T lymphoblasts and CD4+ T cell clones (TCC) from deficient patients displayed a reduced surface FasL expression and resistance to AICD. CD8+ TCC from healthy and deficient patients displayed similar high level of FasL and susceptibility to AICD. In Jurkat CD4+ T cells competent to transduce IFN-γ signaling, IFN-γ induced surface FasL export and their Fas-dependent apoptosis. Effector T cells generated from a patient with a dominant negative mutation of IFN-γR1 (IFN-γR1DN) following stimulation with mycobacterial antigens were unable to kill MHC class II-matched, mycobacterial antigen-pulsed macrophages. Normal Fas expression in T cells and FasL in CD8+ cells may account for the absence of autoimmune disorders in these patients. Conversely, defective FasL expression on IFN-γR1DN CD4+ T cells impairs their cytotoxic functions and highlights a novel role for IFN-γ signaling in the control of mycobacterial infection in humans.

Original languageEnglish
Pages (from-to)2196-2204
Number of pages9
JournalEuropean Journal of Immunology
Volume37
Issue number8
DOIs
Publication statusPublished - Aug 2007

Keywords

  • Apoptosis
  • Bacterial infection
  • Cytokine
  • Human T cells

ASJC Scopus subject areas

  • Immunology

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    Boselli, D., Losana, G., Bernabei, P., Bosisio, D., Drysdale, P., Kiessling, R., Gaston, J. S. H., Lammas, D., Casanova, J. L., Kumararatne, D. S., & Novelli, F. (2007). IFN-γ regulates Fas ligand expression in human CD4+ T lymphocytes and controls their anti-mycobacterial cytotoxic functions. European Journal of Immunology, 37(8), 2196-2204. https://doi.org/10.1002/eji.200636541