Coordinate expression of CC chemokine ligand 5, granulysin, and perforin in CD8+ T cells provides a host defense mechanism against Mycobacterium tuberculosis

F Stegelmann, M Bastian, K Swoboda… - The Journal of …, 2005 - journals.aai.org
F Stegelmann, M Bastian, K Swoboda, R Bhat, V Kiessler, AM Krensky, M Roellinghoff
The Journal of Immunology, 2005journals.aai.org
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 …
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.
journals.aai.org