EXCEED THE SPACE PROVIDED. Infectionwith Toxoplasma gondii continuesto be a serious cause of morbidity and mortality inthe newborns and the immunosuppressedindividuals,especially those infectedwith AIDS. Cell mediated immunity is critical for the host defense, bothduring acute and chronic infectionwith the parasite.Amongst the T cell subtypes, CD8+ T cells are importantmediators of long-term immune response against the infection. The effector/ memory CD8+ T cells play a dominant role in the protectionagainst both challenge infection and reactivationof latent disease. The understandingof the mechanisms involvedin the generation and the maintenanceof robust CD8-I. T cell immunity against T. gondii may enableto generate noveltherapeutic or prophylacticagents against the parasite. Inthe first specific aim we planto evaluatethe development of CD8+T cell immunityagainst T.gondii. The role of NK cells and IL-2 inthe inductionof CD8+T cell responsewill be assayed. The quality of CD8+ T cell responseinthe presence of overwhelmingTH-2 cytokineenvironmentwill be determined. The second specific aim will entail the study of the role of host IL- 15 in the maintenanceof CD8+ T cell memory response against T.gondii. The maintenanceof CD8+ memory T cells inthe IL-15 receptor knock out mice will be studied andthe mechanisticrole of IL-15 in the survival of memory CD8+ T cell responsewill be determined. The third specific aim is to evaluatethe effect of exogenous IL-I5 treatment in preventingthe reactivationof latentT.gondii infection during advanced immunosuppressionusing an experimentalMAIDS (murineacquiredimmunodeficiencysyndrome) model. The preliminarystudies suggest that IL-I5 treatment can delay the reactivationof chronicT.gondii infection even during advancedstages of MAIDS infection.The therapeuticeffect of IL-15 or super-immuneCD8+ T cells from IL-15treatedhost on the dual infectedmice will be studied. PERFORMANCESITE( ========================================Section End===========================================
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