Activation of Tim-3-Galectin-9 pathway improves survival of fully allogeneic skin grafts

Transpl Immunol. 2008 Apr;19(1):12-9. doi: 10.1016/j.trim.2008.01.008. Epub 2008 Feb 20.

Abstract

T cell immunoglobulin and mucin domain (Tim)-3 is a molecule expressed on terminally differentiated murine Th1 cells but not on Th2 cells. Identification of Galectin-9 as a ligand for Tim-3 has now firmly established the Tim-3-Galectin-9 pathway as an important regulator of Th1 immunity, which results in apoptosis of Th1 cells. Here, we demonstrate that engagement of Tim-3 by mouse recombinant Galectin-9 remarkably suppresses allograft rejection and improves survival of allogeneic skin grafts. Furthermore, administration of recombinant Galectin-9 decreases Tim-3 positive cells in draining lymph node and selectively inhibits production of IFN-gamma after skin transplantation. At last, even low dose of Galectin-9 (1 microg/ml) can obviously inhibit TCR crosslinking-induced primary T cell proliferation in vitro. These observations suggest that Tim-3-Galectin-9 pathway plays an important role in the termination of productive Th1-immune response and could lead to developing novel therapies in transplant medicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Galectins / immunology
  • Galectins / metabolism*
  • Galectins / pharmacology
  • Graft Rejection / prevention & control*
  • Graft Survival*
  • Hepatitis A Virus Cellular Receptor 2
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Virus / immunology
  • Receptors, Virus / metabolism*
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • Skin Transplantation / immunology*
  • Th1 Cells / immunology
  • Th1 Cells / metabolism*
  • Th2 Cells / immunology
  • Th2 Cells / metabolism*

Substances

  • Galectins
  • Havcr2 protein, mouse
  • Hepatitis A Virus Cellular Receptor 2
  • Receptors, Antigen, T-Cell
  • Receptors, Virus
  • Recombinant Proteins
  • galectin 9, mouse
  • Interferon-gamma