title: Emergence of NK1.1+ cells as effectors of IFN-gamma dependent immunity to Toxoplasma gondii in MHC class I-deficient mice.
abstract: 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 beta 2m-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 beta 2m-deficient mice induced strong resistance to lethal challenge, with > 50% surviving beyond 3 months. Vaccinated beta 2m-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 beta 2m-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 beta 2m-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.
authors.affiliation: Immunology and Cell Biology Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
authors.forename: E Y
authors.initials: EY
authors.lastname: Denkers
authors.forename: R T
authors.initials: RT
authors.lastname: Gazzinelli
authors.forename: D
authors.initials: D
authors.lastname: Martin
authors.forename: A
authors.initials: A
authors.lastname: Sher
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D003433:Crosses, Genetic; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D005805:Genes, MHC Class I; D007114:Immunization; D007371:Interferon-gamma / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D008212:Lymphocyte Depletion; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014124:Toxoplasmosis, Animal / Q000276:immunology*; D014613:Vaccines, Attenuated; D001613:beta 2-Microglobulin / Q000172:deficiency*
chemical_list: D016827:CD8 Antigens; D014613:Vaccines, Attenuated; D001613:beta 2-Microglobulin; D007371:Interferon-gamma