IFN‐γ regulates Fas ligand expression in human CD4+ T lymphocytes and controls their anti‐mycobacterial cytotoxic functions
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 an...
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Veröffentlicht in: | European journal of immunology 2007-08, Vol.37 (8), p.2196-2204 |
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Sprache: | eng |
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Zusammenfassung: | 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. |
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ISSN: | 0014-2980 1521-4141 |
DOI: | 10.1002/eji.200636541 |