The Specific Aims of this proposal are to examine the influence of IFN-gamma on the development of C. parvum-specific mucosal T (Specific Aim 1) and B (Specific Aim 2) lymphocyte responses in healing C57BL/6J and non-healing IFN-gamma knockout (GKO) mice.
This is a new research proposal aimed at defining the level(s) at which Interferon gamma functions in the establishment of an acquired immune response to the coccidian parasite Cryptosporidium parvum. The hypotheses to be tested are that production of IFN-gamma during an immune response to C. parvum influences the type of parasite-specific T and B lymphocyte responses elicited. The Specific Aims of this proposal are to examine the influence of IFN-gamma on the development of C. parvum-specific mucosal T (Specific Aim 1) and B (Specific Aim 2) lymphocyte responses in healing C57BL/6J and non-healing IFN-gamma knockout (GKO) mice. For Specific Aim 1, C. parvum-specific T cell lines and clones will be derived from the Peyer's patches, mesenteric lymph nodes, lamina propria and intraepithelial compartment of infected healing C57BL/6J and non- healing GKO mice. These T cells will be characterized with respect to phenotype, cytokine profile and in vivo function. The studies outline in Specific Aim 2 combine immunohistochemical, ELISPOT and ELISA techniques to analyze C. parvum-specific IgA responses on both the cellular and protein levels in infected healing C57BL/6J and non-healing GKO mice. The P.I. states that the studies proposed herein represent long-term research goals aimed at enhancing our knowledge of the contribution of IFN-gamma in the generation of an immune response to C. parvum. She adds that the results from these studies will ultimately enhance our understanding of the mechanisms involved in C. parvum protective immunity, providing critical information pertinent to the development of effective immunotherapeutic approaches that may be necessary to resolve otherwise fatal cryptosporidiosis in patients with AIDS. Moreover, it is anticipated that the results obtained should have extended pertinence to the role of IFN-gamma in the development of mucosal immune responses in general.