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As shown previously, a given cytotoxic T lymphocyte (CTL) clone (KB5.C20) could be induced to express the Fas ligand (FasL) by either T cell receptor (TCR) engagement or phorbol 12-myristate 13-acetate (PMA)/ionomycin stimulation. In contrast, another CTL clone (BM3.3) has now been found to exert Fas-based cytotoxicity only after TCR engagement, but not after PMA/ionomycin stimulation. This suggested the existence of a PMA-insensitive, antigen-induced pathway leading to FasL expression. The inability of PMA to promote Fas-based cytotoxicity in BM3.3 cells was correlated with a defect in expression of the classical protein kinase C (PKC) isoforms alpha and beta I. In KB5.C20 cells depleted of PMA-sensitive PKC isoforms and thus no longer responsive to PMA, Fas-based cytotoxicity could still be induced via the TCR/CD3 pathway. On the other hand, a requirement for phosphatidylinositol-3 kinase (PI3K) selectively in this TCR/CD3-induced pathway was demonstrated by specific inhibition with wortmannin. These results suggest that FasL expression when induced via the TCR/CD3 involves PI3K, and when induced by PMA/ionomycin requires the expression of PMA-sensitive PKC isoforms absent in clone BM3.3. Additional data suggest that in neither case was NF-kappa B activation implicated in FasL expression.

Original publication

DOI

10.1002/eji.1830251227

Type

Journal article

Journal

Eur J Immunol

Publication Date

12/1995

Volume

25

Pages

3381 - 3387

Keywords

Androstadienes, Animals, Base Sequence, Clone Cells, Cytotoxicity, Immunologic, Fas Ligand Protein, Gene Expression Regulation, Ionomycin, Isoenzymes, Ligands, Membrane Glycoproteins, Mice, Mice, Inbred CBA, Molecular Sequence Data, NF-kappa B, Phosphatidylinositol 3-Kinases, Phosphotransferases (Alcohol Group Acceptor), Protein Kinase C, RNA, Messenger, Receptors, Antigen, T-Cell, Signal Transduction, T-Lymphocytes, Cytotoxic, Tetradecanoylphorbol Acetate, Wortmannin