The costimulatory role of TIM molecules

Immunol Rev. 2009 May;229(1):259-70. doi: 10.1111/j.1600-065X.2009.00772.x.


The T-cell immunoglobulin domain and mucin domain (TIM) family, including TIM-1, TIM-2, TIM-3, and TIM-4, is a relatively newly described group of molecules with a conserved structure and important immunological functions, including T-cell activation, induction of T-cell apoptosis and T-cell tolerance, and the clearance of apoptotic cells. TIM-1 costimulates T-cell activation and enhances cytokine production. In humans, TIM-1 also serves as a susceptibility gene for allergy and asthma. TIM-3, expressed on T cells and dendritic cells, regulates T-cell apoptosis and immune tolerance. By contrast, TIM-4, which is expressed primarily on antigen-presenting cells and which is a receptor for phosphatidylserine, regulates T-cell activation and tolerance, in part by mediating the uptake and engulfment of apoptotic cells. The TIM molecules thus have surprisingly broad activities affecting multiple aspects of immunology.

Publication types

  • Review

MeSH terms

  • Animals
  • Asthma / immunology
  • Asthma / metabolism
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism
  • Hepatitis A / immunology
  • Hepatitis A / metabolism
  • Humans
  • Immune Tolerance / immunology
  • Lymphocyte Activation*
  • Membrane Proteins / chemistry
  • Membrane Proteins / immunology*
  • Mice
  • Nitrogenous Group Transferases / immunology
  • Nitrogenous Group Transferases / metabolism
  • Protein Structure, Tertiary
  • Signal Transduction / immunology
  • T-Lymphocytes / immunology*


  • Membrane Proteins
  • Nitrogenous Group Transferases