Mucosal Immune Responses During Cryptosporidiosis

Cryptosporidium parvum is a coccidian parasite that infects intestinal and extraintestinal mucosal epithelial cells in humans, cattle and other mammals. C. Parvum causes self-limiting gastroenteric disease in immune competent hosts, but becomes persistent and life-threatening in immunocompromised individuals. Several recent outbreaks of cryptosporidiosis have occurred, primarily in association with water supplies. There is no effective antimicrobial drug available to treat infection, and no vaccine to prevent disease. Development of these remedies will require understanding what is likely a complex series of immune responses to c. Parvum. It will be especially important to distinguish between protective immunity (leading to termination of infection) and an immune response that might contribute to disease. My long-term goals are: 1) identify antigenic epitopes of C. parvum that elicit protective immunity, and 2) determine whether specific epitopes induce immune responses that contribute to clinical disease in susceptible hosts. The research proposed in this application constitutes an important first step toward these goals, because it involves identifying the sequence of immune responses that occur in intestinal mocosa during the course of disease in a susceptible, immune competent host. My hypothesis is that the immune response induced by C. parvum early in infection differs from that which occurs in conjunction with termination of infection. Specific Aims 1. Document the ileal mucosal immune responses that occur during the course of infection. 2. Characterize in vitro responses to C. parvum antigens of lymphocyte collected from local, regional, and systemic immune compartments. 3. Develop T cell clones from lymphocytes taken during the course of infection, and characterize their responses to stimulation with fractionated C. parvum parasites.