Cytotoxicity against Mycobacterium tuberculosis (MTB) infected macrophages may be a mechanism of host defense. Thus, the capacity of alveolar lymphocytes (AL) and alveolar macrophages (AM) from tuberculin skin test positive healthy subjects to serve as cytotoxic T lymphocytes (CTLs) and target cells, respectively, in response to MTB (H37Ra) or purified protein derivative (PPD) was investigated using a 51Cr release assay. AM infected with MTB or stimulated with PPD were targets of blood CTL activity (up to 20% specific cytotoxicity) at effector to target ratios (E:T) of 10:1 and higher (p < 0.01). Blood CTL activity was predominantly restricted to class II MHC and was adhesion (ICAM/LFA-1) molecule dependent AM were, however, more resistant to cytotoxicity than autologous blood monocytes which were targets of CTL activity at lower E:T ratios (1:1) and with greater specific cytotoxicity (to 30%). To examine CTL activity of AL, bronchoalveolar cells were stimulated with PPD plus IL-2 for 7-10 days. AL were cytotoxic for autologous mycobacterial stimulated blood monocytes at E:T ratios of 10:1 and higher (similar to blood lymphocytes) (p < 0.01). CTL activity of AL required cell adhesion molecules and was both class I and class II MHC restricted. Both CD4+ and CD8+ AL were expanded by stimulation with PPD and IL-2. Furthermore, sorting of these phenotypes using antibody coated magnetic beads demonstrated that both CD4+ and CD8+ AL had CTL activity for PPD stimulated and for MTB-infected monocytes. Thus, AL are capable of both Class I and II MHC dependent CTL activity against MTB infected or PPD-stimulated macrophages. Such novel cytotoxic responses may be a major mechanism of defense against MTB at the site of disease activity.
|Original language||English (US)|
|Journal||Journal of Investigative Medicine|
|State||Published - Jan 1 1996|
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)