Human multipotent mesenchymal stromal cells use galectin-1 to inhibit immune effector cells

Human multipotent mesenchymal stromal cells (MSC) suppress proliferation and alloreactivity of T cells. Several signalling molecules and enzymes contribute to this effect. We focused on carbohydrate-protein interactions and investigated if lectins are involved in immune modulation by MSC. Gene expression profiling of MSC revealed that one of the most important lectins in this setting, galectin-1, was highly expressed. Galectin-1 protein was detected intracellularly and on the cell surface of MSC. In addition, galectin-1 was released into the cell culture supernatant by MSC. In order to analyze the functional role of galectin-1, a stable knockdown of galectin-1 in MSC using a retroviral transfection system was established. Galectin-1 knockdown in MSC resulted in a significant loss of their immunomodulatory properties, when compared to MSC infected with non-targeting control sequences. The galectin-1 knockdown partially restored the proliferation of CD4(+) and CD8(+) T cells. By contrast, the effect of MSC on non-alloreactive NK cells was unaffected by downregulation of galectin-1 expression. Furthermore, MSC-derived galectin-1 significantly modulated the release of cytokines involved in GvHD and autoimmunity, e. g. TNFalpha, IFNgamma, IL-2 and IL-10. These results identify galectin-1 as the first lectin mediating the immunomodulatory effect of MSC on allogeneic T cells.