Presentation of galectin-1 by extracellular matrix triggers T cell death

Apoptotic elimination of T cells at sites of inflammation or infiltration into tumors limits an effective immune response. T cell Apoptosis can be initiated by a variety of triggers, including Galectin-1, a soluble, secreted lectin that binds to oligosaccharide ligands on cell surface glycoproteins, or to oligosaccharide ligands on extracellular matrix glycoproteins in tissue stroma. Although Galectin-1 has no transmembrane domain and is secreted from cells that make it, it is not clear if Galectin-1 functions as a soluble death trigger in vivo. We examined the ability of stromal cells secreting Galectin-1 to kill T cells. Although the stromal cells synthesized abundant Galectin-1, the majority of the Galectin-1 remained bound to the cell surface, and stromal cell-associated Galectin-1 killed bound T cells. In contrast, insufficient amounts of functional Galectin-1 were released from the stromal cells into the media to kill T cells in the absence of contact with stromal cells. However, when stromal cells were grown on Matrigel, a mixture of extracellular matrix proteins, or on permeable membranes above Matrigel, secreted Galectin-1 bound to Matrigel and killed T cells without stromal cell contact. Ten-fold less Galectin-1 on Matrigel was sufficient to kill adherent T cells compared with soluble Galectin-1. These results demonstrate that Galectin-1 in extracellular matrix is able to directly kill susceptible T cells. Because increased Galectin-1 deposition in tumor stroma occurs with tumor progression in various types of Cancer, Galectin-1 in stroma may act locally in the apoptotic elimination of infiltrating T cells during an immune response.