Capacity of myeloid and plasmacytoid dendritic cells especially at mature stage to express and secrete HLA-G molecules

Human leukocyte antigen (HLA-G), a class Ib major histocompatibility complex mole- cule, is potentially relevant in the immune response through its various immune cell functions. Its ex- pression noticed in some malignancies has also been shown on macrophages and dendritic cells (DC) in tumoral and inflammatory diseases. As DC constitute a key component in the immune re- sponse, this work aimed at assessing the expression of HLA-G at transcriptional and proteic levels dur- ing differentiation and maturation of the different DC subsets. We show that HLA-G transcription was induced during CD34-derived DC differentiation and is associated with a cell-surface expression in half of cases and with a substantial secretion of soluble HLA-G in all cases. Results were very sim- ilar for monocyte-derived DC, but there was still a weak HLA-G cell-surface expression and a lower level of secretion. On the contrary, HLA-G tran- scription was weak in plasmacytoid DC without any HLA-G cell-surface expression and with a basal level of secretion. The mechanisms involved in HLA-G expression appear transcriptional and post- transcriptional. However, the amount of HLA-G transcripts and the expression of the protein are not related. HLA-G expression or secretion by DC may have negative consequences on the function of effective immune cells and also on DC themselves via the interaction with inhibitory receptors ex- pressed by these cells. The capacity of DC to ex- press or secrete HLA-G should be studied in the context of cellular therapy using DC in addition to its suppressive action in immune response. J. Leu- koc. Biol. 76: 1125-1133; 2004.