Th1-specific Cell Surface Protein Tim-3 Regulates Macrophage Activation and Severity of an Autoimmune Disease

Nature. 2002 Jan 31;415(6871):536-41. doi: 10.1038/415536a.

Abstract

Activation of naive CD4(+) T-helper cells results in the development of at least two distinct effector populations, Th1 and Th2 cells. Th1 cells produce cytokines (interferon (IFN)-gamma, interleukin (IL)-2, tumour-necrosis factor (TNF)-alpha and lymphotoxin) that are commonly associated with cell-mediated immune responses against intracellular pathogens, delayed-type hypersensitivity reactions, and induction of organ-specific autoimmune diseases. Th2 cells produce cytokines (IL-4, IL-10 and IL-13) that are crucial for control of extracellular helminthic infections and promote atopic and allergic diseases. Although much is known about the functions of these two subsets of T-helper cells, there are few known surface molecules that distinguish between them. We report here the identification and characterization of a transmembrane protein, Tim-3, which contains an immunoglobulin and a mucin-like domain and is expressed on differentiated Th1 cells. In vivo administration of antibody to Tim-3 enhances the clinical and pathological severity of experimental autoimmune encephalomyelitis (EAE), a Th1-dependent autoimmune disease, and increases the number and activation level of macrophages. Tim-3 may have an important role in the induction of autoimmune diseases by regulating macrophage activation and/or function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD11 Antigens / immunology
  • Cloning, Molecular
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Female
  • Gene Expression Profiling
  • Hepatitis A Virus Cellular Receptor 2
  • Humans
  • Leukopoiesis
  • Macrophage Activation*
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Sequence Data
  • Rats
  • Rats, Inbred Lew
  • Rats, Sprague-Dawley
  • Receptors, Virus*
  • Th1 Cells / immunology*
  • Th1 Cells / transplantation

Substances

  • CD11 Antigens
  • HAVCR2 protein, human
  • Havcr2 protein, mouse
  • Hepatitis A Virus Cellular Receptor 2
  • Membrane Proteins
  • Receptors, Virus

Associated data

  • GENBANK/AF450241
  • GENBANK/AF450242
  • GENBANK/AF450243