Coordinate expression of CC chemokine ligand 5, granulysin, and perforin in CD8+ T cells provides a host defense mechanism against Mycobacterium tuberculosis.
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.
Stegelmann
Frank
F
Institut für Klinische Mikrobiologie, Immunologie und Hygiene der Friedrich Alexander Universitaet Erlangen-Nuernberg, Erlangen, Germany.
Bastian
Max
M
Swoboda
Kay
K
Bhat
Rauf
R
Kiessler
Viviane
V
Krensky
Alan M
AM
Roellinghoff
Martin
M
Modlin
Robert L
RL
Stenger
Steffen
S
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
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