CD4(+) and CD8(+) T cells kill intracellular Mycobacterium tuberculosis bya perforin and Fas/Fas ligand-independent mechanism

Cytotoxic effector phenotype and function of MHC-restricted Mycobacterium t uberculosis (MTB)-reactive CD4(+) and CD8(+) T lymphocytes were analyzed fr om healthy tuberculin skin test-positive persons. After stimulation in vitr o with MTB, both CD4(+) and CD8(+) T cells up-regulated mRNA expression for granzyme A and B, granulysin, perforin, and CD95L (Fas ligand). mRNA level s for these molecules were greater for resting CD8+ than CD4(+) T cells. Af ter MTB stimulation, mRNA levels were similar for both T cell subsets. Incr eased perforin and granulysin protein expression was confirmed in both in C D4(+) and CD8(+) T cells by flow cytometry. Both T cell subsets lysed MTB-i nfected monocytes. Biochemical inhibition of the granule exocytosis pathway in CD4(+) and CD8(+) T cells decreased cytolytic function by > 90% in both T cell subsets. Ab blockade of the CD95-CD95L interaction decreased cytoly tic function for both T cell populations by 25%. CD4(+) and CD8(+) T cells inhibited growth of intracellular MTB in autologous monocytes by 74% and 84 %, respectively. However, inhibition of perforin activity, the CD95-CD95L i nteraction, or both CTL mechanisms did not affect CD4(+) and CD8(+) T cell mediated restriction of MTB growth. Thus, perforin and CD95-CD95L were not involved in CD4(+) and CD8(+) T cell mediated restriction of MTB growth.