Zhu, C. et al. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat. Immunol. 6, 1245-1252

Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature Immunology (Impact Factor: 20). 01/2006; 6(12):1245-52. DOI: 10.1038/ni1271
Source: PubMed


Tim-3 is a T helper type 1 (T(H)1)-specific cell surface molecule that seems to regulate T(H)1 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(H)1 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(H)1 cells were Tim-3-dependent in vitro, and administration of galectin-9 in vivo resulted in selective loss of interferon-gamma-producing cells and suppression of T(H)1 autoimmunity. These data suggest that the Tim-3-galectin-9 pathway may have evolved to ensure effective termination of effector T(H)1 cells.

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    • "It has been shown that once T helper cells get activated and differentiate into Th1 lineage, they express TIM-3 [47, 48]. IFN-g leads to the upregulation of Galectin-9, which binds to TIM-3 to create a negative co-stimulatory signal promoting Th1 cell death through apoptosis and necrosis [49]. As expected, it has been shown that TIM-3 blockade accelerates Th1-mediated autoimmune disease in rodent models [48]. "
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