Tim-3-Galectin-9 pathway involves the suppression induced by CD4+CD25+ regulatory T cells

Immunobiology. 2009;214(5):342-9. doi: 10.1016/j.imbio.2008.10.007. Epub 2008 Dec 6.

Abstract

CD4(+)CD25(+) regulatory T cells (Tregs) are considered to play a key role as suppressors of immune-mediated reactions. The mechanisms of this suppression in animals and patients with autoimmune, allergic or oncogenic diseases have been investigated under various conditions. However, the precise mode of suppression by CD4(+)CD25(+) Tregs is still not clear. In this report, Tim-3-Galectin-9 pathway was explored as one of the mechanisms for the suppression and cytotoxicity induced by Tregs. Here, we demonstrated that Galectin-9 was expressed on CD4(+)CD25(+) Tregs by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Interestingly, blocking Tim-3-Galectin-9 pathway resulted in an obvious decreased suppression activity of Tregs and enhanced Th1 cytokine level in vitro. Furthermore, blocking Tim-3-Galectin-9 pathway negated prolonged survival of allogeneic skin grafts induced by CD4(+)CD25(+) Tregs in vivo. Our results suggest that Tim-3-Galectin-9 pathway involves the function of CD4(+)CD25(+) Tregs.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibodies, Blocking
  • Galectins / genetics
  • Galectins / immunology*
  • Galectins / metabolism*
  • Graft Rejection / immunology*
  • Hepatitis A Virus Cellular Receptor 2
  • Immune Tolerance / immunology
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Interleukin-4 / metabolism
  • Lymphocyte Activation
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Receptors, Virus / genetics
  • Receptors, Virus / immunology*
  • Receptors, Virus / metabolism*
  • Signal Transduction
  • Skin Transplantation
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / pathology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th1 Cells / pathology
  • Transplantation Immunology

Substances

  • Antibodies, Blocking
  • Galectins
  • Havcr2 protein, mouse
  • Hepatitis A Virus Cellular Receptor 2
  • Interleukin-2
  • Membrane Proteins
  • Receptors, Virus
  • Timd2 protein, mouse
  • galectin 9, mouse
  • Interleukin-4
  • Interferon-gamma