Immunoregulation in sarcoidosis. Perpetual secretory dysfunction of natural killer-like cells.

Sarcoidosis is an immunopathogenic disorder of uncertain cause. Because the regulation of monocyte mobilization and function may be critical to granuloma formation in this disease, we evaluated production of the cell-directed inhibitor of monocyte leukotaxis (CDI-MLx) by peripheral blood and bronchoalveolar lavage mononuclear cells from these patients. Cells obtained from either source during clinically active disease spontaneously produced this leukotactic regulator in vitro in amounts comparable to those achieved with maximal mitogenic stimulation of normal cells. Plasma leukotactic inhibitory activity and spontaneous inhibitor production were significantly associated. Plasma inhibitory activity and CDI-MLx production were normal in patients whose disease was inactive. Spontaneous production continued for at least 7 days in vitro and could not be attributed to alterations in the absolute numbers of specific mononuclear cell populations. Partitioning of peripheral blood mononuclear cells by a combination of E-rosetting and immunoadherence techniques indicated, however, that CDI-MLx was produced by a subpopulation of natural killer-like cells that formed E-rosettes and bore the OKMI and Leu 7 membrane antigens.