MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I AND CLASS-II DEFICIENT KNOCK-OUT MICE ARE RESISTANT TO PRIMARY BUT SUSCEPTIBLE TO SECONDARY EIMERIA-PAPILLATA INFECTIONS

Two distinct mechanisms seem to function in reducing oocyst output dur ing Eimeria papillata infections in mice. For naive mice, immunity was afforded by a T-cell-independent gamma-interferon (IFN-gamma) respons e mediated by natural killer (NK) cells. On reinfection, resistance wa s associated with T-cells and, to a lesser extent, perforin. To determ ine if antigen presentation with major histocompatibility complex (MHC ) molecules was required to control oocyst production by NK cells duri ng primary infection or by T-cells during secondary infection, mutant mice that lacked H2-IA beta b (A beta b(-/-)) or beta 2-microglobulin (beta 2m(-/-)) were used. Since MHC molecules are required for the mat uration of alpha beta T-cells, A beta b(-/-) and beta 2m(-/-) mutant m ice are also deficient in functional alpha beta(+)CD4(+) or alpha beta (+)CD8(+) T-cells, respectively. As compared with wild-type control mi ce, oocyst output by mutant mice was not significantly affected during primary infection, suggesting that the ability of NK cells to control parasite replication is not dependent on the expression of MHC molecu les. On reinfection, differences were observed for mutant mice as comp ared with controls. A beta b(-/-) mice were found to be more susceptib le than beta 2m(-/-) mice, suggesting that the alpha beta(+)CD4(+) T-c ell subset plays a greater role in resistance to reinfection than does the alpha beta(+)CD8(+) T-cell subset. The mechanism of resistance de pends on the immune status of the host and requires the coordinated in teraction of both alpha beta(+) T-cell subsets for optimal parasite co ntrol during subsequent infections.