The long-term objective is to analyze the potential role of a recently-identified novel mechanism of T cell-mediated activation of macrophage antileishmanial effects in host defense in vivo. This mechanism of activation involves antigen-specific interactions between effector T cells and infected macrophages, interactions that are neither lymphokine-mediated nor involve cytotoxicity to host cells. Different well-studied murine models of leishmaniasis will be investigated in an effort to establish whether a correlation exists between the in vitro expression of the lymphokine-independent activation mechanism (referred to as """"""""contact-mediated"""""""") and resolution of infection in mice. As a corollary, the possibility that suppressor cells (or their soluble products) from BALB/c mice with disseminated L. major infections can down-regulate expression of the effector T cells in vitro will be explored. In related studies, lymphokine-mediated and cell contact-mediated mechanisms of macrophage activation will be compared for their dependence on an oxidative burst to impart an antileishmanial effect in vitro, and for their influence on phagolysosomal pH. Finally, the murine macrophage activation assay will be adapted to human cell cultures to permit subsequent clinical studies. These studies of a novel T cell-mediated mechanism activation of macrophage antimicrobial defense can be expected to have direct relevance to leishmaniasis as well as have potentially important implications for understanding host defense to certain other intracellular pathogens. Since this novel defenes mechanism involves a subclass of murine lymphocytes analogous to those infected by HIV in humans, results of this line of investigation could bear on infectious complications in patients with AIDS.
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