CHARACTERIZATION OF SUPPRESSOR FUNCTION OF HUMAN ALVEOLAR MACROPHAGESFOR T-LYMPHOCYTE RESPONSES TO PHYTOHEMAGGLUTININ - CELLULAR SELECTIVITY, REVERSIBILITY, AND EARLY EVENTS IN T-CELL ACTIVATION

The predominant immunoregulatory activity of alveolar macrophages (AM) on T lymphocytes is to suppress their responses to antigenic and mito genic stimuli. The suppressive activity of human AM for T cell respons es to phytohemagglutinin (PHA) was further characterized. At ratios of AM to T lymphocytes of 0.4:1 to 1.6:1, AM inhibited the blastogenic r esponse (H-3-thymidine uptake into DNA) to PHA by 26 to 87%, respectiv ely. Blood monocytes precultured in vitro for 5 to 7 days inhibited re sponses to PHA similarly. Freshly isolated blood monocytes, peritoneal macrophages, and A-549 epithelial and CCD18Lu fibroblast cell lines f ailed to inhibit T lymphocyte responses. AM were capable of suppressin g PHA-induced blastogenesis of purified CD4 cells without die addition of other cells. Cell contact was required for suppression of CD4 cell s, as demonstrated using dual chambers. T cells precultured with AM wi th or without PHA retained the ability to respond to PHA compared with control T cells not precultured with AM. Kinetic experiments showed t hat AM needed to be added at the initiation of a 3-day culture period for suppression to occur. Analysis of the T cell DNA cycle revealed th at AM decreased the percentage of cells entering the synthesis phase o f DNA production. Flow cytometry also was used to assess the effect of AM on early markers of T cell activation. AM inhibited the percentage of T cells expressing the interleukin-2 receptor 46 to 83% and the tr ansferrin receptor 58 to 78% at 24 to 48 h after stimulation with PHA. There was no effect of AM on expression of HLA-DR. Therefore, suppres sion of T cell responses to PHA by AM was a selective property of AM, required cell contact, and was expressed directly on CD4 cells. Suppre ssion by AM was reversible and occurred at an early stage in the T cel l cycle. These results demonstrate that AM are uniquely adapted to dow nregulate cellular immune responses in the lung.