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 functio n: CD4(-) CD8(-) double-negative (DN) CTL lyse susceptible targets via Fas- Fas ligand interaction and CD8(+) CTL via the granule exocytosis pathway. C D8(+) CTL, but not DN CTL, can mediate an antimicrobial activity against My cobacterium tuberculosis-infected target cells that is dependent on cytotox ic granules that contain granulysin. We investigated the role of nuclear ap optosis 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 caspas e independent, However, both DN and CD8(+) CTL-induced nuclear apoptosis re quired caspase activation. More important, the antimicrobial effector funct ion of CD8(+) CTL was not diminished by inhibition of caspase activity. The se data indicate that target cell nuclear apoptosis is not a requirement fo r CTL-mediated killing of intracellular M. tuberculosis.