Augmentation of the CD8+ T Cell Response by IFN-γ in IL-12-Deficient Mice During Toxoplasma gondii Infection

Abstract

The importance of IFN-γ in regulating the host CD8+ T cell response during microbial infection has not been delineated. Mice deficient for the p40 chain of the IL-12 heterodimer have impaired IFN-γ production and are susceptible to infection with the intracellular parasite Toxoplasma gondii. The administration of exogenous IFN-γ to parasite-infected p40−/− mice increases survival and up-regulates the depressed CD8+ T cell response following infection. CD8+ T cells isolated from cytokine-treated p40−/− mice exhibit an increase in both precursor CTL frequency and IFN-γ production compared with untreated controls. The enhancement of the CD8+ T cell response is independent of CD4+ T cell help. These CD8+ T cells induce protective immunity against a lethal challenge when adoptively transferred into naive p40−/− and IFN-γ−/− mice. These observations indicate that IFN-γ can regulate the CD8+ T cell response during T. gondii infection.