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

21 Citations (Scopus)

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

Fingerprint

Fas Ligand Protein
T-Lymphocytes
Cell Death
Antigens
Clone Cells
Apoptosis
Infection Control
Macrophages
Mutation

Keywords

  • Apoptosis
  • Bacterial infection
  • Cytokine
  • Human T cells

ASJC Scopus subject areas

  • Immunology

Cite this

IFN-γ regulates Fas ligand expression in human CD4+ T lymphocytes and controls their anti-mycobacterial cytotoxic functions. / Boselli, Daniela; Losana, Giuliana; Bernabei, Paola; Bosisio, Daniela; Drysdale, Pamela; Kiessling, Rolf; Gaston, John S H; Lammas, David; Casanova, Jean Laurent; Kumararatne, Dinakantha S.; Novelli, Francesco.

In: European Journal of Immunology, Vol. 37, No. 8, 08.2007, p. 2196-2204.

Research output: Contribution to journalArticle

Boselli, D, Losana, G, Bernabei, P, Bosisio, D, Drysdale, P, Kiessling, R, Gaston, JSH, Lammas, D, Casanova, JL, Kumararatne, DS & 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, vol. 37, no. 8, pp. 2196-2204. https://doi.org/10.1002/eji.200636541
Boselli, Daniela ; Losana, Giuliana ; Bernabei, Paola ; Bosisio, Daniela ; Drysdale, Pamela ; Kiessling, Rolf ; Gaston, John S H ; Lammas, David ; Casanova, Jean Laurent ; Kumararatne, Dinakantha S. ; Novelli, Francesco. / IFN-γ regulates Fas ligand expression in human CD4+ T lymphocytes and controls their anti-mycobacterial cytotoxic functions. In: European Journal of Immunology. 2007 ; Vol. 37, No. 8. pp. 2196-2204.
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