The role of endogenous regulatory T cells in acute and chronic immune response to experimental murine Trypanosoma cruzi infection
Kotner, Joshua Steven
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Infection with the parasite Trypanosoma cruzi results in a robust and multi-faceted host immune response. The acute phase rarely results in death because the primary immune response is usually sufficient to control parasitemia. However, sterile cure of infection seldom follows, leading to a persistent infection by low numbers of parasites that live intracellularly in muscle and nerve tissue forming the basis for chronic disease. The exact mechanisms of initial or eventual immune evasion and parasite persistence in muscle tissue are unknown. CD8+ T cells can kill host-cells harboring intracellular parasites, and are therefore important in immune control of T. cruzi infection. Recently, our lab reported that in T. cruzi-infected mice CD8+ T lymphocytes that infiltrate chronically-infected muscle tissue become dysfunctional as judged by their inability to secrete gamma interferon (IFN- ) or lyse target cells in vitro. Chronic or persistent parasite infections may be the result of the immune system mounting an incompetent immune response, or due to suppression of an appropriate response, which can be induced by regulatory T cells and exploited by the parasite as an immune evasion mechanism. Understanding the mechanisms of initial T. cruzi immune evasion and CD8+ T cell dysfunction in chronically-infected muscle tissue could lead to new therapeutic strategies to combat Chagas’ disease. The overall goal of this study is to investigate the role that “natural” CD4+CD25+ regulatory T cells play in modulating both acute and chronic immune responses to T. cruzi infection.