Immune responses, and in particular the cytokine response of CD4+ and CD8+ T cells, to T. cruzi correlates inversely with the presence of severe disease during chronic T. cruzi infection. This hypothesis is supported by numerous studies in experimental animals and by our previous work showing that individuals in the G0 and G1 clinical groups have range of T. cruzi-specific T cell responses while those in the G3 group are almost very low responders. We propose a longitudinal study that will follow individuals who initially exhibit no signs of disease and evaluate the progression of the disease symptoms in correlation with their anti-parasite cellular immune responses over the 5-year project period. In addition, we will observe both untreated and drug-treated patients for evidence of cure. These patients will be evaluated to determine if cure associates with the qualitative and quantitative characteristics of the anti T. cruzi T cell response prior to cure and if the success of treatment to induce cure is associated with the anti-parasite response prior to or after treatment. Collection of these data will provide insights into the strength of the association between cellular immuninty, parasite load and disease development, determine the changes, if any, in cellular immune responses and parasite load over a five year follow-up period, and significantly expand our knowledge of cellular immune responses in chronic chagasic patients. Completion of these studies will also provide valuable information on the relationship between cellular immune responses and cure in human patients and on the immunological consequences of drug treatment. These data will be useful for assessing what constitutes an effective immune response in T. cruzi infection, thereby guiding our vaccine development program and providing insight into how to most effectively treat chronically infected individuals.