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

Nat Immunol. 2005 Dec;6(12):1245-52. doi: 10.1038/ni1271. Epub 2005 Nov 13.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cells, Cultured
  • Down-Regulation / physiology*
  • Female
  • Galectins / physiology*
  • Glycoproteins / metabolism
  • Hepatitis A Virus Cellular Receptor 2
  • Immunity, Cellular
  • Interferon-gamma / biosynthesis
  • Ligands
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Sequence Data
  • Protein Binding
  • Receptors, Virus / metabolism*
  • Receptors, Virus / physiology
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism


  • Galectins
  • Glycoproteins
  • Havcr2 protein, mouse
  • Hepatitis A Virus Cellular Receptor 2
  • LGALS9 protein, human
  • Ligands
  • Receptors, Virus
  • Interferon-gamma