The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity

Abstract

Tim-3 is a T helper type 1 (T_H1)–specific cell surface molecule that seems to regulate T_H1 responses and the induction of peripheral tolerance. However, the identity of the Tim-3 ligand and the mechanism by which this ligand inhibits the function of effector T_H1 cells remain unknown. Here we show that galectin-9 is the Tim-3 ligand. Galectin-9-induced intracellular calcium flux, aggregation and death of T_H1 cells were Tim-3-dependent in vitro, and administration of galectin-9 in vivo resulted in selective loss of interferon-γ-producing cells and suppression of T_H1 autoimmunity. These data suggest that the Tim-3–galectin-9 pathway may have evolved to ensure effective termination of effector T_H1 cells.