Apoptosis in Toxoplasma gondii activated T cells: The role of IFN gamma in enhanced alteration of Bcl-2 expression and mitochondrial membrane potential

摘要

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-IFN gamma 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-IFN gamma mAb. These findings provide further insight into the mechanisms of T cell apoptosis in T. gondii infection.