title: Coordinate expression of CC chemokine ligand 5, granulysin, and perforin in CD8+ T cells provides a host defense mechanism against Mycobacterium tuberculosis.
abstract: 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.
authors.affiliation: Institut für Klinische Mikrobiologie, Immunologie und Hygiene der Friedrich Alexander Universitaet Erlangen-Nuernberg, Erlangen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Stegelmann
authors.forename: Max
authors.initials: M
authors.lastname: Bastian
authors.forename: Kay
authors.initials: K
authors.lastname: Swoboda
authors.forename: Rauf
authors.initials: R
authors.lastname: Bhat
authors.forename: Viviane
authors.initials: V
authors.lastname: Kiessler
authors.forename: Alan M
authors.initials: AM
authors.lastname: Krensky
authors.forename: Martin
authors.initials: M
authors.lastname: Roellinghoff
authors.forename: Robert L
authors.initials: RL
authors.lastname: Modlin
authors.forename: Steffen
authors.initials: S
authors.lastname: Stenger
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis*; D001782:Blood Donors; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D018946:Chemokine CCL5; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D018613:Microscopy, Confocal; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D014376:Tuberculosis / Q000276:immunology
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; C483024:CCL5 protein, human; D018946:Chemokine CCL5; D019742:Chemokines, CC; C075005:GNLY protein, human; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin