Modulation of IL-15 expression by IFN-gamma in human monocytes

IL-15 shares many biological activities with IL-2 but unlike IL-2, which is secreted by T cells, IL-15 mRNA is expressed in monocytes, fibroblasts and epithelial cell lines. Althought it has been difficult to demonstrate secretion of IL-15 protein in the supernatants. We investigated the expression of IL-15 by human monocytes upon activation with IFN-gamma. By semiquantitative RT-PCR we found that IFN-gamma stimulation of human monocytes augmented the expression of IL-15 at the mRNA level but did not induce IL-15 protein protein release in supernatants, as measured by ELISA or CTLL assay. Instead, flow cytometry analysis of monocytes stained with an anti-IL-15 mAb (M112) revealed surface expression of the cytokine. Untreated monocytes expressed low levels of IL-15 on their cell surface; but treatment with IFN-gamma induced a 5-7 fold increase of membrane-associated IL-15. Acidic treatment of monocytes did not elute IL-15 from cells indicating that IL-15 is probably covalently linked to membrane surface. These results indicate that monocytes that fail to secrete IL-15 may express this cytokine on the cell-surface.