There is little known regarding human T lymphocyte responses to T. cruzi antigens, or of the nature of T cell responses from patients with different clinical phases of infection. The goals of this proposal are to examine human T cell responses to recombinant and native antigens of T. cruzi. This will include analysis of cytokine profiles of T cells that respond to these antigens, as well as analysis of T. cruzi antigens potentially involved in resistance or autoimmunity. We have described the importance of macrophage activation mediated by GM-CSF and IFN-gamma, as well as macrophage deactivation, mediated by TGF-beta and IL-10 in mice. The current proposal will extend these observations to humans, by evaluating the production of cytokines which are associated with beneficial type response (IL-2, IFN-gamma, GM-CSF) as well with those which may be associated with pathological responses (IL-4, IL-5, IL-10 and TGF-beta) in different clinical forms of human T. cruzi infection. We will also evaluate recombinant and native T. cruzi antigens for their ability to elicit these types of cytokine responses from different patient groups.
