CTL-mediated killing of intracellular Mycobacterium tuberculosis is independent of target cell nuclear apoptosis.
Two subsets of human CTL have been defined based upon phenotype and function: CD4(-) CD8(-) double-negative (DN) CTL lyse susceptible targets via Fas-Fas ligand interaction and CD8(+) CTL via the granule exocytosis pathway. CD8(+) CTL, but not DN CTL, can mediate an antimicrobial activity against Mycobacterium tuberculosis-infected target cells that is dependent on cytotoxic granules that contain granulysin. We investigated the role of nuclear apoptosis for the antimicrobial effector function of CD1-restricted CTL using the caspase inhibitor N:-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone. We found that DN CTL-induced target cell lysis was completely dependent on caspase activation, whereas the cytolytic activity of CD8(+) CTL was caspase independent. However, both DN and CD8(+) CTL-induced nuclear apoptosis required caspase activation. More important, the antimicrobial effector function of CD8(+) CTL was not diminished by inhibition of caspase activity. These data indicate that target cell nuclear apoptosis is not a requirement for CTL-mediated killing of intracellular M. tuberculosis.
Thoma-Uszynski
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Division of Dermatology, Department of Microbiology and Immunology and Molecular Biology Institute, University of California, Los Angeles, School of Medicine, Los Angeles, CA 90095, USA.
Stenger
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Modlin
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D017209:Apoptosis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000382:microbiology; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology / Q000276:immunology* / Q000382:microbiology; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D007424:Intracellular Fluid / Q000276:immunology / Q000382:microbiology; D019169:Jurkat Cells; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology / Q000382:microbiology; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology / Q000276:immunology* / Q000382:microbiology*
D020169:Caspases