IMMUNITY TO CRYPTOSPORIDIOSIS IN SIV INFECTED MACAQUES

Tufts University Boston, Boston MA

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Abstract

This is the first resubmission of a research proposal in response to PA- 97-030 that focuses on defining the immunologic parameters involved in the development of chronic cryptosporidiosis in individuals with AIDS. The hypothesis to be tested is that a loss in mucosal CD4+ T cells and subsequent dysfunction of the mucosal associated immune system is responsible for chronic cryptosporidiosis in individuals with AIDS. To accomplish this, we will use a rhesus macaque model. Specific Aim 1 will examine the susceptibility of macaques to the development of chronic cryptosporidiosis at different stages of SIV infection. Specific Aim 2A of this proposal will examine the T and B lymphocyte responses associate with resolution of an acute Cryptosporidium parvum infection in normal, immunocompetent macaques. These studies will utilize FACS analysis, immunohistochemistry, ELISA, in vitro proliferative assays and RT-PCR analysis to examine the humoral response and the phenotype, cytokine profile and proliferative response of mucosal and peripheral T lymphocytes in non-SIV infected macaques with resolving cryptosporidiosis. Specific Aim 2B of this proposal will determine if there are quantitative and/or qualitative differences in T and/or B lymphocyte responses that are associated with the development of chronic cryptosporidiosis in SIV-infected macaques. These studies will utilize the same techniques listed above for Specific Aim 2A to examine the humoral response and the phenotype, cytokine profile and proliferative response of mucosal and peripheral T lymphocytes in SIV-infected macaques with acute and chronic cryptosporidiosis. The studies proposed herein represent long term research goals aimed at enhancing our knowledge of the immune mechanism(s) involved in the control of cryptosporidiosis, and the underlying reasons for failure in the SIV/HIV-infected host. An understanding of this mechanism is important for the derivation of immunotherapeutic strategies that may be necessary to control chronic cryptosporidiosis in patients with AIDS.