Augmentation of the CD8+ T cell response by IFN-γ in IL-12-deficient mice during Toxoplasma gondii infection

The importance of IFN-gamma 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-gamma production and are susceptible to infection with the intracellular parasite Toxoplasma gondii. The administration of exogenous ITN-gamma 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-gamma 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-gamma(-/-) mice. These observations indicate that IFN-gamma can regulate the CD8(+) T cell response during T. gondii infection.