Importance of CD8+Vβ8+ T cells in IFN-γ-mediated prevention of toxoplasmic encephalitis in genetically resistant BALB/c mice

In our attempt to identify a major T cell population(s) that recognizes protective Toxoplasma gondii antigens and produces interferon-gamma (IFN-gamma) for prevention of toxoplasmic encephalitis (TE), we found T cell receptor V beta 8(+) cells to be the most frequent IFN-gamma-producing population infiltrated into the brain of T. gondii-infected BALB/c mice genetically resistant to the disease. To examine the role of IFN-gamma production by this T cell population for resistance, we transferred V beta 8(+) immune T cells purified from spleens of infected BALB/c and IFN-gamma(-/-) mice into infected, sulfadiazine-treated, athymic nude mice. After discontinuation of sulfadiazine treatment, control nude mice that had not received any T cells and animals that had received V beta 8(+) T cells from IFN-gamma(-/-) mice all died because of reactivation of infection (TE). In contrast, animals that had received the cells from BALB/c mice survived. Thus, IFN-gamma production by V beta 8(+) T cells plays an important role in prevention of TE in these animals. When V beta 8(+) immune T cells were divided into CD4(+) and CD8(+) subsets, a potent protective activity was observed only in the CD8+ subset, whereas a combination of both subsets provided greater protection than did the CD8(+)V beta 8(+) population alone. These results indicate that the CD8(+) subset of V beta 8(+) T cells is a major afferent limb of IFN-gamma-mediated resistance of BALB/c mice against TE, although the CD4(+) subset of the T cell population works additively or synergistically with the CD8(+)V beta 8(+) population.