Granule-dependent cytolysis of Mycobacterium tuberculosis-infected macrophages by human γδ+ T cells has no effect on intracellular mycobacterial viability
J. S. Passmore,
R. H. Glashoff,
P. T. Lukey,
S. R. Ress,
J. S. Passmore
Clinical Immunology Laboratory, Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Observatory, Cape Town, South Africa and
Search for more papers by this authorR. H. Glashoff
Clinical Immunology Laboratory, Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Observatory, Cape Town, South Africa and
Search for more papers by this authorP. T. Lukey
GlaxoSmithKline Medicines Research Centre, Stevenage, Hertfordshire, UK
Search for more papers by this authorS. R. Ress
Clinical Immunology Laboratory, Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Observatory, Cape Town, South Africa and
Search for more papers by this authorJ. S. Passmore,
R. H. Glashoff,
P. T. Lukey,
S. R. Ress,
J. S. Passmore
Clinical Immunology Laboratory, Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Observatory, Cape Town, South Africa and
Search for more papers by this authorR. H. Glashoff
Clinical Immunology Laboratory, Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Observatory, Cape Town, South Africa and
Search for more papers by this authorP. T. Lukey
GlaxoSmithKline Medicines Research Centre, Stevenage, Hertfordshire, UK
Search for more papers by this authorS. R. Ress
Clinical Immunology Laboratory, Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Observatory, Cape Town, South Africa and
Search for more papers by this author Prof. S.R. Ress, Clinical Immunology Laboratory, Department of Medicine, H47 Old Main Building, University of Cape Town Medical School, Observatory 7925, Cape Town, South Africa. E-mail: [email protected]
Abstract
One of the most important effector functions of activated γδ+ T cells in tuberculosis is their strong cytolytic activity against a variety of target cells, including M. tuberculosis-infected macrophages. In the present study, we investigated the relationship between the mechanism of cytolysis utilized by γδ+ CTL and intracellular M. tuberculosis survival using a panel of cytolytic human M. tuberculosis-specific γδ+ CTL clones. Cytolysis mediated by the γδ+ T-cell clones was found to be Ca2+-dependent, sensitive to Cyclosporin A, and was completely abrogated following Sr2+-induced de-granulation of the γδ+ T cell effectors. These data demonstrate that γδ+ T-cell-mediated cytoxicity was mediated via the granule exocytosis/perforin pathway. Despite significant cytolytic activity against mycobacteria infected U937 cells, the γδ+ CTL clones had no impact on the survival of intracellular M. tuberculosis.
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