Stimulation of human peripheral blood mononuclear cells with live Mycobacterium bovis BCG activates cytolytic CD8+ T cells in vitro.
Experimental data have shown that Mycobacterium tuberculosis can survive within the host cell and in doing so may release secreted antigen into the endogenous antigen-processing pathway. If mycobacterial antigen can gain access to MHC class I molecules then CD8+ T cells may play a role in host defence against M. tuberculosis infection. To identify whether there is a role for the CD8+ T cell in mycobacterial infection we have stimulated peripheral blood mononuclear cells (PBMC) from bacillus Calmette-Guérin (BCG) vaccinated individuals with live M. bovis BCG. The activation state of the T cells was established by staining for the interleukin-2 (IL-2) receptor (CD25), HLA-DR or the transferrin receptor (CD71). Using FACScan analysis we have shown that, in vitro, live M. bovis BCG activates significantly more CD8+ T cells in comparison to the soluble antigen purified protein derivative (PPD). In addition, live M. bovis BCG activates more CD8+ T cells than a non-viable preparation of the same M. bovis BCG following irradiation. The function of the activated CD8+ T cells was addressed using positively selected cells in a cytotoxic T-cell assay. CD8+ T cells isolated from a 7-day M. bovis BCG-stimulated PBMC culture were shown to be cytolytic against target cells infected with live M. bovis BCG, dead M. bovis BCG, and to a lesser extent, PPD. These results suggest that CD8+ T cells may be activated by stimulation with live mycobacteria, and that this subset can play a cytolytic role in the immune response to mycobacterial infections.
Turner
J
J
Department of Clinical Sciences, London School of Hygiene and Tropical Medicine, UK.
Dockrell
H M
HM
D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D001500:BCG Vaccine / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D008213:Lymphocyte Activation; D009163:Mycobacterium bovis / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000942:Antigens, Bacterial; D001500:BCG Vaccine