Pneumocystis carinii pneumonia (PcP) is an infection that occurs widely in hosts with suppressed immune systems. It is clear that CD4+ cells play a central role in host defense against this opportunistic pathogen. However, it is likely that redundancy in some mechanisms of cellular immune defense occurs in the host, specifically in the CD8+ lineage of T-cells. Since HIV-infected individuals have reduced CD4+ cell numbers, but increased or sustained levels of CD8+ T cells, it is proposed that by stimulating the anti-Pc and immunomodulatory capacities of the CD8+ cells in CD4+-depleted PcP-infected hosts, the outcome of PcP-infected individuals should improve. To test these hypotheses, the following specific aims are proposed: (1) determine whether cytokine products of CD8+ T cells activate alveolar macrophages for phagocytosis and killing of Pc in vitro; (2) determine whether CD8+ T cells are cytotoxic towards Pc alone or in association with alveolar macrophages in vitro; (3) determine ability of immunization with Pc to increase CD8+ T cell responses and decrease infection in vivo; and (4) determine the ability of transfer of Pc-elicited CD8+ T cells to modulate infection in vivo.

R01HL057011

1997-04-01

2002-03-31