EMERGENCE OF NK1.1+ CELLS AS EFFECTORS OF IFN-GAMMA DEPENDENT IMMUNITY TO TOXOPLASMA-GONDII IN MHC CLASS-I-DEFICIENT MICE

CD8+ T lymphocytes have been reported to play a major role in the protective immune response against acute infection with Toxoplasma gondii. In order to further assess the role of CD8+ cells in resistance against this protozoan we examined the ability of beta2m-deficient mice, which fail to express MHC class I molecules and peripheral CD8+ lymphocytes, to survive tachyzoite challenge following vaccination with an attenuated parasite mutant. Surprisingly, vaccination of beta2m-deficient mice induced strong resistance to lethal challenge, with >50% surviving beyond 3 months. Vaccinated beta2m-deficient mice, but not control heterozygotes, showed a five- to six-fold expansion in spleen cell number and approximately 40% of the splenocytes were found to express the NK markers NK1.1 and asialo GM1. Spleen cells from the vaccinated beta2m-deficient animals failed to kill either infected host cells or the NK target YAC-1. However, high levels of IFN-gamma were secreted when the cells were cultured in vitro with soluble T gondii lysate, and this response was abolished by NK1.1+ but not CD4+ and CD8+ lymphocyte depletion, implicating the NK1.1+ population as the major source of IFN-gamma. More importantly, vaccine-induced immunity in beta2m-deficient mice was completely abrogated by in vivo administration of antibody to NK1.1, asialo GM1, or IFN-gamma. Together, the data suggest that in class I-deficient mice vaccinated against T gondii, the absence of CD8+ effector cells is compensated for by the emergence of a population of NK1.1+ and asialo GM1+ cells which lack cytolytic activity, and that the protective action of these cells against the parasite is attributable to IFN-gamma production. The induction of this novel NK population may provide an approach for controlling opportunistic infections in immunocompromised hosts.