Emerging Tim-3 functions in antimicrobial and tumor immunity

Trends Immunol. 2011 Aug;32(8):345-9. doi: 10.1016/j.it.2011.05.003. Epub 2011 Jun 21.

Abstract

T cell immunoglobulin-3 (Tim-3) has been identified as a marker of differentiated interferon-γ-producing CD4(+) T helper type 1 and CD8(+) T cytotoxic type 1 cells. The interaction of Tim-3 with its ligand, galectin-9 (Gal-9), induces cell death, and in vivo blockade of this interaction results in exacerbated autoimmunity and abrogation of tolerance in experimental models, establishing Tim-3 as a negative regulatory molecule. Recent studies have uncovered additional mechanisms by which Tim-3 negatively regulates T cell responses, such as promoting the development of CD8(+) T cell exhaustion and inducing expansion of myeloid-derived suppressor cells. In contrast to this inhibitory effect on T cells, Tim-3-Gal-9 interaction promotes macrophage clearance of intracellular pathogens. Here, we focus on the emerging role for Tim-3 in tumor and antimicrobial immunity.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • Apoptosis
  • Bacterial Infections / immunology*
  • Galectins / immunology*
  • Galectins / metabolism
  • Hepatitis A Virus Cellular Receptor 2
  • Humans
  • Immune Tolerance / genetics
  • Immunity, Cellular
  • Immunity, Innate
  • Immunosuppression
  • Macrophage Activation
  • Membrane Proteins / immunology*
  • Myeloid Cells / immunology
  • Neoplasms / immunology*
  • Th1 Cells / immunology*

Substances

  • Antigens, Neoplasm
  • Galectins
  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 2
  • LGALS9 protein, human
  • Membrane Proteins