TRANSFORMING GROWTH-FACTOR-BETA-1 (TGF-BETA-1) DOWN-REGULATES IGA FC-RECEPTOR (CD89) EXPRESSION ON HUMAN MONOCYTES

IgA is the predominant immunoglobulin in human secretions and the seco nd most important immunoglobulin in the circulation on a quantitative basis. The clearance of IgA is dependent on the function of at least t hree types of receptors. One of these receptors recognizes the Fc port ion of the IgA molecule, Fc alpha R, which has been cloned recently. F c alpha R, also designated CD89, is found on a number of cells, includ ing human glomerular mesangial cells, and monocytes. In this study we analysed the effect of TGF-beta 1, a cytokine with strong immunosuppre ssive function, on the expression of CD89 on freshly isolated monocyte s. We found that TGF-beta 1 down-regulates CD89 expression on human pe ripheral blood monocytes in a dose-dependent fashion. Optimal down-reg ulation occurred at a concentration of 5 ng/ml. The down-regulation of CD89 by TGF-beta 1 is linear in time, with a mean down-regulation of 34 +/- 13% after 24 h. Also at the mRNA level, CD89 expression was dow n-regulated by TGF-beta 1, suggesting regulation of CD89 at the transc riptional level. Monocytes pre-treated with TGF-beta 1 displayed a red uced response to IgA, as measured by IL-6 production by monocytes, in contrast to monocytes pre-treated with medium alone. These results sug gest an important role for TGF-beta 1 in the regulation of CD89. This down-regulation may have direct consequences for the handling of IgA b y human monocytes.