1. Antigen-induced cell death of T effector cells in vitro proceeds via the Fas pathway, requires endogenous interferon-gamma and is independent of perforin and granzymes.
- Author
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Sobek V, Balkow S, Körner H, and Simon MM
- Subjects
- Animals, Antibodies, Monoclonal pharmacology, Antigens, Viral immunology, CD3 Complex immunology, Concanavalin A pharmacology, Exocytosis, Fas Ligand Protein, Granzymes, Lymphocyte Activation drug effects, Lymphocytic Choriomeningitis immunology, Lymphocytic choriomeningitis virus immunology, Male, Mice, Mice, Inbred C3H, Mice, Inbred C57BL, Perforin, Pore Forming Cytotoxic Proteins, Serine Endopeptidases physiology, Tumor Necrosis Factor-alpha antagonists & inhibitors, Tumor Necrosis Factor-alpha physiology, Antigens immunology, Apoptosis physiology, Interferon-gamma physiology, Membrane Glycoproteins physiology, T-Lymphocyte Subsets cytology, fas Receptor physiology
- Abstract
Activation of resting T cells usually leads to their proliferation and differentiation into effector cells and a subsequent decline following elimination of the antigen. A situation of excessive antigen density may result in T cell receptor (TCR)-induced deletion of T effector cells, a process termed antigen-induced cell death (AgICD). Previous studies indicate that AgICD of cytotoxic T cells may be induced by either of the two key cytotoxic processes, granule exocytosis, including perforin and granzymes, or the Fas ligand (FasL)/Fas pathway. By using in vitro-polyclonally activated or ex vivo-derived virus-induced T cell populations from mice with mutations or targeted gene defects in one or more components of the two key cytolytic pathways we now show that TCR-induced apoptosis is only impaired in the absence of FasL and/or Fas, but not in the absence of perforin and/or granzymes. Furthermore, antibody-blockage of FasL alone is sufficient to inhibit early T cell death. Inhibition of both, FasL and tumor necrosis factor (TNF-alpha) is required to abrogate late apoptosis by AgICD. The fact that antibodies to IFN-gamma also inhibit AgICD suggests that the perforin plus granzyme-independent and FaSL and/or TNF-alpha facilitated process of AgICD of T effector cells is tightly regulated by endogenous IFN-gamma.
- Published
- 2002
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