Importance of CD8 + Vβ8 + T Cells in IFN-γ-Mediated Prevention of Toxoplasmic Encephalitis in Genetically Resistant BALB/c Mice

Abstract

In our attempt to identify a major T cell population(s) that recognizes protective Toxoplasma gondii antigens and produces interferon-γ (IFN-γ) for prevention of toxoplasmic encephalitis (TE), we found T cell receptor Vβ8⁺ cells to be the most frequent IFN-γ-producing population infiltrated into the brain of T. gondii-infected BALB/c mice genetically resistant to the disease. To examine the role of IFN-γ production by this T cell population for resistance, we transferred Vβ8⁺ immune T cells purified from spleens of infected BALB/c and IFN-γ^−/− 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 Vβ8⁺ T cells from IFN-γ^−/− mice all died because of reactivation of infection (TE). In contrast, animals that had received the cells from BALB/c mice survived. Thus, IFN-γ production by Vβ8⁺ T cells plays an important role in prevention of TE in these animals. When Vβ8⁺ 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⁺Vβ8⁺ population alone. These results indicate that the CD8⁺ subset of Vβ8⁺ T cells is a major afferent limb of IFN-γ-mediated resistance of BALB/c mice against TE, although the CD4⁺ subset of the T cell population works additively or synergistically with the CD8⁺Vβ8⁺ population.