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.
He
Jiale
J
Department of Pathology, UCLA School of Medicine, Los Angeles, California 90095, USA.
Baum
Linda G
LG
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D016466:CHO Cells; D002448:Cell Adhesion; D002450:Cell Communication; D002455:Cell Division; D002460:Cell Line; D006224:Cricetinae; D005109:Extracellular Matrix / Q000378:metabolism*; D037483:Galectin 1 / Q000031:analogs & derivatives* / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000378:metabolism; D012995:Solubility; D017154:Stromal Cells / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*
D037483:Galectin 1; C445499:LGALS1 protein, human; D011994:Recombinant Proteins