Nature Immunology 6, 1245 - 1252 (2005)
Published online: 13 November 2005; | doi:10.1038/ni1271
The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunityChen Zhu1, Ana C Anderson1, Anna Schubart1, Huabao Xiong2, Jaime Imitola1, Samia J Khoury1, Xin Xiao Zheng3, Terry B Strom3
& Vijay K Kuchroo11
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. 2
Immunobiology Center, Mount Sinai School of Medicine of New York University, New York, New York 10029, USA. 3
Division of Immunology and Transplant Research Center, Beth Israel and Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Correspondence should be addressed to Vijay K Kuchroo vkuchroo@rics.bwh.harvard.edu 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- -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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