Cryptosporidium parvum is an important gastrointestinal pathogen around the world. C. parvum causes severe diarrhea and not infrequently death among the immunologically naive and the immunocompromised, particularly AIDS patients. Control measures for cryptosporidiosis are currently underdeveloped as chemotherapeutic approaches have so far proven unsuccessful. The main objective of this project is to study enteric T cell-modulated immune responses to C. parvum using a novel murine model of infection. This approach may identify mechanisms of host resistance which can be further exploited to devise strategies aimed to control cryptosporidiosis. We plan to test the hypothesis that immunological control of cryptosporidiosis is achieved through gut-associated CD4+ TH2- mediated cellular and humoral responses. Specific approaches to be taken to define protective immunity to this infection will include: 1. Generate C. parvum-specific, MHC-restricted, CD4+ and CD8+ murine T cell clones. 2. Selectively reconstitute C. parvum-infected athymic nude mice with CD4+ and CD8+ T cell clones to determine which clones provide resistance. 3. Examine the functional gut-associated immune responses in reconstituted nude mice resistant to C. parvum infections. Thus we will identify the T cell type(s) which influence the appropriate mucosally-relevant effector mechanisms to control cryptosporidiosis. The knowledge gained is likely to be greatly beneficial to the high percentage of AIDS patients and children worldwide that suffer cryptosporidiosis, since it could established the basis for optimizing effective immunotherapeutic interventions to treat this currently untreatable infection.
