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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI039203-05
Application #
2887128
Study Section
Special Emphasis Panel (SRC (47))
Program Officer
Sager, Polly R
Project Start
1995-09-30
Project End
2001-08-31
Budget Start
1999-09-01
Budget End
2001-08-31
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Arizona
Department
Veterinary Sciences
Type
Schools of Earth Sciences/Natur
DUNS #
City
Tucson
State
AZ
Country
United States
Zip Code
85721