Antileishmanial host defense depends largely if not exclusively on cell mediated immune mechanisms. The goal of this project is to study a novel mechanism of activation of antileishmanial defense in macrophages that is T cell mediated but apparently distinct from activation due to conventional lymphokines. Specifically, this work will attempt to assess the relative role of this defense mechanism in vivo. It will also test the hypothesis that the activation signals are integral components of the effector T cell plasma membrane. To establish homogeneous cell populations for further analysis of this defense, T cell clones will be derived from mice with resolving Leishmania major infections. These clones will be slected for their ability to activate macrophages for antileishmanial defense in vitroby lymphokine dependent and independent mechanisms. Antigen specificity and genetic restriction of these T cell clone functions will be assessed. Using adoptive transfer of selected clones, we will attempt to define the role of particular T cell populations in protective immunity. T-T hybridomas will be prepared from selected T cell clones and plasma membrane preparations from the hybridomas will be analyzed for their ability to activate antileishmanial defense in macrophages in a specific manner. These studies may aid in the future identification of membrane components that participate in T cell activation in antileishmanial defense, in addition to providing a new strategy for development of an antileishmanial vaccine. Validation of the apparently novel defense mechanism could have broad implications for cell-mediated host defense to a variety of intracellular pathogens.
| Sypek, J P; Matzilevich, M M; Wyler, D J (1991) Th2 lymphocyte clone can activate macrophage antileishmanial defense by a lymphokine-independent mechanism in vitro and can augment parasite attrition in vivo. Cell Immunol 133:178-86 |
| Sypek, J P; Wyler, D J (1991) Antileishmanial defense in macrophages triggered by tumor necrosis factor expressed on CD4+ T lymphocyte plasma membrane. J Exp Med 174:755-9 |
| Sypek, J P; Wyler, D J (1990) T-cell hybridomas reveal two distinct mechanisms of antileishmanial defense. Infect Immun 58:1146-52 |
