ALVEOLAR MACROPHAGES .3. STUDIES ON THE MECHANISM OF INHIBITION OF T-CELL PROLIFERATION

Abstract

Unlike macrophages from the peritoneal cavity or the peripheral blood, rat alveolar macrophages actively inhibit mitogen-induced T [thymus-derived] cell proliferation. Studies on the characteristics of this inhibitory activity revealed the following: the macrophages must be alive, but mitomycin C does not block their activity; they must be added to lymphocyte cultures soon after the initiation of the cultures, and prolonged pre-incubation of macrophages in vitro diminishes their cytostatic activity; suppressive activity is most obvious in cultures of rapidly proliferating lymphocytes and the lymphocytes themselves may be syngeneic or allogeneic; the suppressive activity may be duplicated by a low MW dialysable component of macrophage culture supernatants and suppression of RNA synthesis is a readily demonstrable as suppression of DNA synthesis in target cells; the cytostatic effects of alveolar macrophages in lymphocyte cultures do not appear to result from target cell destruction. Repeated endobronchial lavage of rats revealed the presence of 2 alveolar macrophage subpopulations, 1 (weakly adherent in vivo) supportive to T lymphocyte proliferation, and another (strongly adherent) strongly inhibitory; the latter population comprises the majority of alveolar macrophages in normal rats.