Augmentation of the CD8+ T cell response by IFN-gamma 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 IFN-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.
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Department of Physiology, Dartmouth Medical School, Lebanon, NH 03756, USA.
Kasper
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Khan
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D000276:Adjuvants, Immunologic / Q000502:physiology*; D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D004198:Disease Susceptibility; D015536:Down-Regulation; D005260:Female; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D018664:Interleukin-12 / Q000172:deficiency* / Q000235:genetics; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D013234:Stem Cells / Q000276:immunology; D013696:Temperature; D013997:Time Factors; D014122:Toxoplasma / Q000145:classification / Q000235:genetics / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000235:genetics* / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control; D014611:Vaccination
D000276:Adjuvants, Immunologic; D018664:Interleukin-12; D007371:Interferon-gamma