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The Tim-3 Ligand Galectin-9 Negatively Regulates T Helper Type 1 Immunity

C. Zhu, A. Anderson, Annette Schubart, H. Xiong, J. Imitola, Samia J Khoury, Xin Xiao Zheng, T. Strom, V. Kuchroo
Published 2005 · Biology, Medicine

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Tim-3 is a T helper type 1 (TH1)–specific cell surface molecule that seems to regulate TH1 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 TH1 cells remain unknown. Here we show that galectin-9 is the Tim-3 ligand. Galectin-9-induced intracellular calcium flux, aggregation and death of TH1 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 TH1 autoimmunity. These data suggest that the Tim-3–galectin-9 pathway may have evolved to ensure effective termination of effector TH1 cells.
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