Modulation of the immunoregulatory functions of alveolar macrophages in cell-mediated immune responses

Studies on the immunoregulatory functions of alveolar macrophages (AM) in cell-mediated immune (CMI) responses have revealed that their suppressive effect is a time-dependent activity which is exerted during the afferent phase of immune activation and is fully developed within 48 hr of culture initiation. We have extended these studies to an investigation of the ability of various immunomodulators which enhance T-cell activation to alter the immunoregulatory functions of AM. Treatment of cultures with PMA, a phorbol ester which acts as a co-stimulant to promote accelerated cellular activation, abrogated the dose- and time-dependent suppressive effect of AM in CMI. Treatment with a mild oxidizing agent, sodium periodate, completely reversed AM-mediated suppression as well as augmented their accessory function in CMI. Furthermore, addition of IL-2 to T-cell cultures incubated with AM resulted in significant enhancement of the generation of cytotoxic effector lymphocytes; however, the presence of lymphokine or indomethacin alone could only partially influence the immunoregulatory functions of AM in CMI. In contrast, treatment of cultures with a combination of IL-2 and indomethacin completely reversed AM-mediated suppression of CMI. These results indicate that the immunoregulatory functions of AM in cell-mediated immune responses are subject to modulation by biologically-active agents which are capable of bringing about an accelerated activation of T-cells and that this observation may have potential therapeutic application.