Granule-dependent cytolysis of Mycobacterium tuberculosis-infected macrophages by human gammadelta+ T cells has no effect on intracellular mycobacterial viability.
One of the most important effector functions of activated gammadelta+ 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 gammadelta+ CTL and intracellular M. tuberculosis survival using a panel of cytolytic human M. tuberculosis-specific gammadelta+ CTL clones. Cytolysis mediated by the gammadelta+ T-cell clones was found to be Ca2+-dependent, sensitive to Cyclosporin A, and was completely abrogated following Sr2+-induced de-granulation of the gammadelta+ T cell effectors. These data demonstrate that gammadelta+ T-cell-mediated cytoxicity was mediated via the granule exocytosis/perforin pathway. Despite significant cytolytic activity against mycobacteria infected U937 cells, the gammadelta+ CTL clones had no impact on the survival of intracellular M. tuberculosis.
Passmore
J S
JS
Clinical Immunology Laboratory, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Glashoff
R H
RH
Lukey
P T
PT
Ress
S R
SR
D002118:Calcium / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D002999:Clone Cells; D003593:Cytoplasm / Q000382:microbiology; D003601:Cytotoxicity Tests, Immunologic; D005089:Exocytosis; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008264:Macrophages / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000502:physiology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D022142:Secretory Vesicles / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*; D020298:U937 Cells
D016692:Receptors, Antigen, T-Cell, gamma-delta; D002118:Calcium