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Coordinate Expression of CC Chemokine Ligand 5, Granulysin, and Perforin in CD8⁺ T Cells Provides a Host Defense Mechanism against Mycobacterium tuberculosis¹

Frank Stegelmann^*, Max Bastian^*, Kay Swoboda^*, Rauf Bhat^*, Viviane Kiessler^*, Alan M. Krensky, Martin Roellinghoff^*, Robert L. Modlin and Steffen Stenger^2,*

^* Institut für Klinische Mikrobiologie, Immunologie und Hygiene der Friedrich Alexander Universitaet Erlangen-Nuernberg, Erlangen, Germany; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305; and Division of Dermatology, Department of Microbiology and Immunology, and Molecular Biology Institute, University of California School of Medicine, Los Angeles, CA 90095

The ability of CD8⁺ T cells to kill intracellular pathogens depends upon their capacity to attract infected cells as well as their secretion of cytolytic and antimicrobial effector molecules. We examined the Ag-induced expression of three immune effector molecules contained within cytoplasmic granules of human CD8⁺ T cells: the chemokine CCL5, the cytolytic molecule perforin, and the antimicrobial protein granulysin. Macrophages infected with virulent Mycobacterium tuberculosis triggered the expression of CCL5 in CD8⁺ T cells only in donors with previous exposure to the tuberculosis bacteria, not in naive donors. Functionally, CCL5 efficiently attracted M. tuberculosis-infected macrophages, but failed to exert direct antibacterial activity. Infected macrophages also triggered the expression of granulysin in CD8⁺ T cells, and granulysin was found to be highly active against drug-susceptible and drug-resistant M. tuberculosis clinical isolates. The vast majority of CCL5-positive cells coexpressed granulysin and perforin. Taken together, this report provides evidence that a subset of CD8⁺ T cells coordinately expresses CCL5, perforin and granulysin, thereby providing a host mechanism to attract M. tuberculosis-infected macrophages and kill the intracellular pathogen.

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