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J Immunol ; 160(5): 2374-9, 1998 Mar 01.
Article in English | MEDLINE | ID: mdl-9498779

ABSTRACT

CTL, both CD4+ and CD8+, are essential in the eradication of intracellular pathogens. Data generated using murine T cells have suggested a critical role for CD95 (Fas, Apo-1) in CD4+ T cell-induced apoptosis of target cells. In contrast, CD8+ CTL predominantly use the perforin/granzyme lytic pathway. At present little is known about the mechanism of CD4+ CTL lytic function during intracellular infection in humans. We have used human CD4+ T cells specific for purified protein derivative (PPD) of Mycobacterium tuberculosis to explore whether CD95 is the dominant cytolytic mechanism. PPD-reactive CD4+ clones efficiently lysed Ag-pulsed autologous monocytes, adherent macrophages, and EBV-transformed B cells. Addition of an antagonistic CD95 Ab had a minimal effect on cytolysis, whereas addition of MgEGTA to block perforin/granzyme resulted in complete inhibition of killing. In contrast, lysis of activated peripheral blood B cells could be partially blocked with the antagonistic CD95 Ab. Supporting these observations, monocytes, macrophages, and EBV-transformed B cells were not lysed by an agonistic CD95 Ab. Activated B cells were readily lysed by the agonistic CD95 Ab. T cell clones triggered through the TCR with anti-CD3 were capable of lysing the CD95-sensitive Jurkat T cell line in a CD95-dependent manner, but were also able to release granzymes. We conclude that human CD4+ T cells are capable of lysing PPD-pulsed targets using both perforin/granzyme and CD95 pathways. The contribution of CD95 is strictly dependent on target cell susceptibility to CD95-mediated killing.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Cytotoxicity, Immunologic , T-Lymphocytes, Cytotoxic/immunology , Tuberculin/immunology , fas Receptor/physiology , Antibodies, Blocking/pharmacology , CD4-Positive T-Lymphocytes/enzymology , Cell Line , Clone Cells , Cytotoxicity Tests, Immunologic , Epitopes/immunology , Esterases/metabolism , Fas Ligand Protein , Humans , Jurkat Cells , Lymphocyte Activation/genetics , Macrophages/immunology , Membrane Glycoproteins/genetics , Monocytes/immunology , Perforin , Pore Forming Cytotoxic Proteins , RNA, Messenger/biosynthesis , T-Lymphocytes, Cytotoxic/enzymology , fas Receptor/biosynthesis , fas Receptor/immunology
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