The investigator proposes to test the hypothesis that binding of CD40L on activated T cells to CD40+ on infected epithelial cells contributes to immunity against Cryptosporidium parvum (Cp) in the biliary tree and the intestine. The investigator proposes to investigate the mechanisms by which CD40-CD40L interactions contribute to Cp immunity by determining whether: 1. CD40L is required for the afferent or efferent limb of Cp specific immunity by transfers of Cp immune and non-immune cells into Cp infected MHC matched knockout recipients. 2. The intact genes for gamma-IFN, TNFR, and/or IL 12 are required for sclerosis of bile ducts in Cp infected mice. 3. The synthesis of Bcl-series proteins is inhibited on a cell-specific basis by Cp infection. If the investigator shows that Cp can be eliminated from the biliary tree by non-specific as well as specific T-cell mediated responses, a subsequent clinical study in AIDS patients, using discriminant analysis, would be planned.
| Ponnuraj, E M; Hayward, A R (2002) Requirement for TNF-Tnfrsf1 signalling for sclerosing cholangitis in mice chronically infected by Cryptosporidium parvum. Clin Exp Immunol 128:416-20 |
| Hayward, A R; Chmura, K; Cosyns, M (2000) Interferon-gamma is required for innate immunity to Cryptosporidium parvum in mice. J Infect Dis 182:1001-4 |
