HUMAN ALVEOLAR T-LYMPHOCYTE RESPONSES TO MYCOBACTERIUM-TUBERCULOSIS ANTIGENS - ROLE FOR CD4(-CELLS AND RELATIVE RESISTANCE OF ALVEOLAR MACROPHAGES TO LYSIS() AND CD8(+) CYTOTOXIC T)

T cell-mediated cytotoxicity against Mycobacterium tuberculosis (MTB)- infected macrophages may be a major mechanism of specific host defense , but little is known about such activities in the lung. Thus, the cap acity of alveolar lymphocyte MTB-specific cell lines (AL) and alveolar macrophages (AM) from tuberculin skin test-positive healthy subjects to serve as CTL and target cells, respectively, in response to MTB (H3 7Ra) or purified protein derivative (PPD) was investigated. Mycobacter ial Ag-pulsed AM were targets of blood CTL activity at E:T ratios of g reater than or equal to 30:1 (Cr-51 release assay), but were significa ntly more resistant to cytotoxicity than autologous blood monocytes. P PD- plus IL-2-expanded AL and blood lymphocytes were cytotoxic for aut ologous mycobacterium-stimulated monocytes at E:T ratios of greater th an or equal to 10:1. The CTL activity of lymphocytes expanded with PPD was predominantly class II MHC restricted, whereas the CTL activity o f lymphocytes expanded with PPD plus IL-2 was both class I and class I I MHC restricted. Both CD4(+) and CD8(+) T cells were enriched in BL a nd AL expanded with PPD and IL-2, and both subsets had mycobacterium-s pecific CTL activity. Such novel cytotoxic responses by CD4(+) and CD8 (+) T cells may be a major mechanism of defense against MTB at the sit e of disease activity.