PROFILES OF HEALING AND NONHEALING CRYPTOSPORIDIUM-PARVUM INFECTION IN C57BL 6 MICE WITH FUNCTIONAL B-LYMPHOCYTES AND T-LYMPHOCYTES - THE EXTENT OF GAMMA-INTERFERON MODULATION DETERMINES THE OUTCOME OF INFECTION/

This study describes healing and nonhealing models of Cryptosporidium parvum infection,vith adult mice that have functional T and B lymphocy tes. In our nonhealing model, mice on a C57BL/6 background which have a targeted disruption in the gamma interferon (IFN-gamma) gene (GKO mi ce) are utilized. C. parvum-infected GKO mice shed extremely high leve ls of oocysts and displayed overwhelming infection of the entire small intestine. The majority of these mice succumbed within 2 to 3 weeks d ue to severe acute infection and profound mucosal destruction. In our healing murine model, C57BL/6J mice treated,vith a single injection of the neutralizing anti-IFN-gamma monoclonal antibody XMG 1.2 prior to infection were used. These mice developed two peaks of oocyst shedding but were ultimately free of parasites on day 30 of infection. Again, the small intestine was the primary site of infection. Mesenteric lymp h node (MLN) cells isolated from C. parvum-infected nonhealing GKO mic e proliferated and secreted interleukin 2 (IL-2) but not IFN-gamma or IL-4 in response to ex vivo restimulation with intact C. parvum sporoz oites or a C. parvum sporozoite antigen preparation. In contrast, para site-specific MLN cells isolated from healing C57BL/6J mice secreted I L-2 and IFN-gamma but not IL-4. These results suggest that IFN-gamma, either directly or indirectly, is important for resistance to and reso lution of crgptosporidiosis. Moreover, these models now allow the anal ysis of parasite-specific cell-mediated and humoral mucosal immune res ponses to determine what constitutes protective immunity to C. parvum.