Host defences to Listeria monocytogenes in mice are mediated by specifically sensitized T lymphocytes (T cells) that enhance the activity of non-specific effector mechanisms, primarily macrophages. Listerial infection in mice is the prototype for cell-mediated immunity to infection, yet the mechanism of this immunity is incompletely understood. We hypothesize that T lymphocytes mediate immune host defenses by increasing the capacity to form granulomas at sites of infection and by stimulating resident and inflammatory macrophage killing function. The capacity to form granulomas requires both the production of monocytes in bone marrow and the movement of monocytes into infected tissues. To test this hypothesis, we plan to generate antigen specific T cell clones and investigate their function. T cell clones will be recovered from mice immune to Listeria, expanded with listerial antigen and phenotyped by surface antigens and histocompatibility restriction. Clones will be selected for their capacity to transfer immunity to Listeria to non-immune mice. The specific function of individual clones that can transfer immunity will then be determined by investigating macrophage function in Listeria- infected mice receiving cloned T cells or supernatants from clones. Specifically, in vivo phagocytic function, number of macrophage progenitor cells, macrophage-colony stimulating factor concentration, monocyte numbers, and granuloma formation will be determined. In addition, the effect of clone supernatants will also be measured in vitro on Kupffer cell and peritoneal macrophage surface membrane markers, metabolism, directed chemotaxis and antimicrobial activity. The results of these studies should indicate how specific T cell clones enhance innate host defense mechanisms to increase resistance. Potential findings will have wide implication for our understanding of how immune host defenses function and suggest ways of manipulating host defenses during infection.
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