Characterization of Suppressor Function of Human Alveolar Macrophages for T Lymphocyte Responses to Phytohemagglutinin: Cellular Selectivity, Reversibility, and Early Events in T Cell Activation

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Abstract
The predominant immunoregulatory activity of alveolar macrophages (AM) on T lymphocytes is to suppress their responses to antigenic and mitogenic stimuli. The suppressive activity of human AM for T cell responses 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 response (3H-thymidine uptake into DNA) to PHA by 26 to 87%, respectively. Blood monocytes precultured in vitro for 5 to 7 days inhibited responses to PHA similarly. Freshly isolated blood monocytes, peritoneal macrophages, and A-549 epithelial and CCD-18Lu fibroblast cell lines failed to inhibit T lymphocyte responses. AM were capable of suppressing PHA-induced blastogenesis of purified CD4 cells without the addition of other cells. Cell contact was required for suppression of CD4 cells, as demonstrated using dual chambers. T cells precultured with AM with or without PHA retained the ability to respond to PHA compared with control T cells not precultured with AM. Kinetic experiments showed that 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 that AM decreased the percentage of cells entering the synthesis phase of 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 transferrin receptor 58 to 78% at 24 to 48 h after stimulation with PHA. There was no effect of AM on expression of HLA-DR.(ABSTRACT TRUNCATED AT 250 WORDS)