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Abstract
Trypanosoma cruzi establishes life-long persistent infection in most mammalian hosts and is the causative agent of Chagas disease in humans. The development of persistent intracellular infection is frequently attributed to the functional compromise of pathogen-specific CD8+ T cells during chronic viral and protozoal infections. CD8+ T cells are crucial for the survival of the acute phase of T. cruzi infection, but the ability of these cells to retain their functional capacity over time is often questioned. This work shows that neither CD8+ T cell regulation nor failed responses, during chronic infection, can explain T. cruzi persistence. In fact, T. cruzi-specific CD8+ T cells continue to function as potent effectors, demonstrated by the in situ production of key effector molecules. In addition, antibody-mediated depletion reveals that CD8+ T cells are crucial for the suppression of parasite outgrowth during chronic infection. Because T. cruzi establishes persistent infection in muscle, despite the maintenance of functional parasite-specific CD8+ T cells in that tissue, the ability of CD8+ T cells to recognize T. cruzi infected cells was in question. The data herein suggest that overexpression of muscle MHC class I increases skeletal muscle surveillance by CD8+ T cells. This initially has a positive impact on T. cruzi control, but ultimately results in the systemic compromise of T. cruzi-specific CD8+ T cells. These data suggest that normal muscle MHC I expression is at a level which permits Trypanosoma cruzi control and the preservation of anti-parasite CD8+ T cell function; a balance which may come at the expense of infection resolution.