Microb Pathog. 2009 Sep 10. [Epub ahead of print]
Apoptosis in Toxoplasma gondii activated T cells: The role of IFNgamma in enhanced alteration of Bcl-2 expression and mitochondrial membrane potential
Begum-Haque S, Haque A, Kasper LH.
Department of Medicine and Microbiology, Dartmouth Medical School Hanover, NH 03755.
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.
PMID: 19748565 [PubMed - as supplied by publisher]