CD8+T Cells in Muscle During Chronic T. cruzi Infection

University Of Georgia (Uga), Athens GA

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Abstract

DESCRIPTION (provided by the applicant): The purpose of this research is to examine some of the immunological mechanisms that contribute to the persistence of T. cruzi in muscle. My hypothesis is that T. cruzi-specific CD8+ T cells fail to clear infection because they have sub-optimal activity at sites of chronic infection. To test this I will: 1. Determine the effect of tissue localization on CD8+ T cell phenotype during T. cruzi infection. I predict that memory CD8+ T cells isolated from the muscle tissue where T. cruzi persists, unlike those from other nonlymphoid tissues, will have attenuated effector function. CD8+ T cells isolated from muscle tissue, liver and spleen will be compared for their ability to kill infected cells and/or produce IFN-gamma in response to infected cells or parasite antigens. 2. Compare antigen-specific and bulk CD8+ T cell development in muscle during T. cruzi infection. I hypothesize that although the bulk CD8+ T cell population in muscle contributes to the tissue destruction and inflammation, parasite-specific CD8+ T cells in that tissue are selectively inactivated or deleted. This would explain why CD8+ T cells are present in such large numbers at the sites of chronic infection, yet are unable to clear T. cruzi from the tissue. To test this I will track parasite-specific T cells using Class I MHC tetramers, and test tetramer-positive cells for functional capacity and signs of apoptosis. I will also adoptively transfer T. cruzi-specific CD8+ T cells from TCR transgenic mice into naive recipients and infect with T. cruzi. At various time points after infection I will assess the location, cell-surface phenotype and effector function of these cells.