The long-term goal of the proposed research is to analyze factors which influence the ability of neonates to resist infectious agents and to be vaccinated successfully against them. Infection with the protozoan parasite Toxoplasma gondii will be used as a model system. Neonatal mice possess a mechanism, dependent on Thy-1+ CD4-CD8- cells and IFN-gamma, that allows a majority of them to survive the acute phase of a primary infection with the protozoan parasite T. gondii. Mice that survive neonatal T. gondii infection exhibit resistance to rechallenge with highly virulent parasites as adults, but the level of protection is inferior to that of adult-immunized controls. Using T. gondii infection as a model system we will (1) analyze the cells and cytokines produced by neonates to learn more about their protective capabilities, (2) analyze how cells and positive and negative regulatory cytokines induced during a primary acute infection in neonatal mice affect the generation of acquired resistance expressed in adults, and (3) analyze acquired immunity in mice vaccinated as neonates and adults to determine the basis for the lesser resistance expressed by neonatally immunized mice.
