Apoptosis in Toxoplasma gondii activated T cells: the role of IFNgamma in enhanced alteration of Bcl-2 expression and mitochondrial membrane potential.
In the present study we addressed the question whether Toxoplasma gondii could promote apoptosis in T lymphocytes in the acute stage of infection. Using in vivo activated T cells and then culturing them for a short time, we observed activation-induced cell death in T. gondii infected mice. A higher level of activation-induced cell death (AICD) was seen in susceptible C57BL/6 mice than in resistant CBA/J mice following infection with the same P strain of parasite. Apoptosis in T cells of susceptible mice was associated with altered induction of Bcl-2/Bax, loss of Mitochondrial Transmembrane Potential. Both CD4+ and CD8+ T cells were found to be susceptible to apoptosis; CD4+ T cells were sensitive to Fas-mediated death whereas CD8+ T cells were insensitive to this signal. Caspase inhibitors had less effect on DNA fragmentation in CD4+ compared to CD8+ T cells. Exposure of CD4+ T cells to anti-IFNgamma mAb resulted in an increase in the number of T cells that were positive for anti-apoptotic molecule Bcl-2 and DiOC6, a cationic dye that accumulates in intact mitochondria. These changes were less noticeable in CD8+ T cells following treatment with anti-IFNgamma mAb. These findings provide further insight into the mechanisms of T cell apoptosis in T. gondii infection.
Begum-Haque
Sakhina
S
Department of Medicine and Microbiology, Dartmouth Medical School Hanover, Lebanon, NH 03755, USA.
Haque
Azizul
A
Kasper
Lloyd H
LH
D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D053938:DNA Fragmentation; D005260:Female; D007371:Interferon-gamma / Q000276:immunology*; D008213:Lymphocyte Activation; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008928:Mitochondria / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology*
D019253:Proto-Oncogene Proteins c-bcl-2; D007371:Interferon-gamma