ALVEOLAR MACROPHAGES FROM HUMANS AND RODENTS SELECTIVELY INHIBIT T-CELL PROLIFERATION BUT PERMIT T-CELL ACTIVATION AND CYTOKINE SECRETION

Alveolar macrophages (AM) are thought to play a key role in the regula tion of immune responses within the lung. While it is well established that AM inhibit T-cell proliferation in vitro, it is unclear whether other aspects of the T-cell activation process are also inhibited. The present study demonstrates that AM from rat, mouse and human differ m arkedly in the potency with which they inhibit mitogen-induced T-cell proliferation, although in humans the degree of inhibition approaches that observed in the animal systems, if antigen (as opposed to mitogen ) is employed as the T-cell activating agent. Rodent and human AM also differ in the mechanisms employed to achieve this inhibition; rodent AM appear to utilize reactive nitrogen intermediates, while this does not appear to be the case for human AM. Despite these differences, T c ells stimulated in the presence of AM display a similar phenotype in a ll species examined, i.e. CD3 down-modulation, up-regulation of interl eukin-2 receptor (IL-2R) expression and IL-2 production, but inability to respond to IL-2. Thus, AM appear to allow T-cell activation and ex pression of T-cell effector function, while selectively inhibiting T-c ell proliferation.