The role of T lymphocytes in pulmonary microbial defense mechanisms.

Understanding how lung immunity develops against pulmonary pathogens should lead to more rational approaches in vaccine design and to the use of recombinant cytokines in lung disease. T lymphocytes are central to the development of effective immune responses; therefore, understanding how lung immunity develops will require a study of how and where T cells respond to respiratory antigens. Our laboratory has helped define the phenotype and function of lung dendritic cells, which likely play an essential role in stimulating naive T cells to respond to antigens. We found that both interstitial and alveolar macrophages can regulate the function of these cells, the former to enhance activity, the latter to suppress. In addition, we developed a murine pulmonary infection model using the fungus, Cryptococcus neoformans, in which T-cell-mediated immunity is essential for effective host clearance of the organism. The role of T cells in this model is to recruit and activate effector cells to resolve the lung infection; both CD4 and CD8 T-cell subsets are required for optimal effector cell recruitment. These studies are summarized as examples of current approaches to understanding pulmonary immunity.