TIM-4 is the ligand for TIM-1, and the TIM-1-TIM-4 interaction regulates T cell proliferation

Nat Immunol. 2005 May;6(5):455-64. doi: 10.1038/ni1185. Epub 2005 Mar 27.


The newly identified TIM family of proteins is associated with regulation of T helper type 1 (T(H)1) and T(H)2 immune responses. TIM-1 is genetically linked to asthma and is a receptor for hepatitis A virus, but the endogenous ligand of TIM-1 is not known. Here we show that TIM-4, which is expressed by antigen-presenting cells, is the ligand for TIM-1. In vivo administration of either soluble TIM-1-immunoglobulin (TIM-1-Ig) fusion protein or TIM-4-Ig fusion protein resulted in hyperproliferation of T cells, and TIM-4-Ig costimulated T cell proliferation mediated by CD3 and CD28 in vitro. These data suggest that the TIM-1-TIM-4 interaction is involved in regulating T cell proliferation.

Publication types

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

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • Cell Proliferation / drug effects
  • Cricetinae
  • Female
  • Hepatitis A Virus Cellular Receptor 1
  • Humans
  • Immunoglobulins / pharmacology
  • Ligands
  • Membrane Proteins / immunology
  • Membrane Proteins / isolation & purification
  • Membrane Proteins / metabolism*
  • Membrane Proteins / pharmacology
  • Mice
  • Protein Binding
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Th2 Cells / drug effects
  • Th2 Cells / immunology


  • Havcr1 protein, mouse
  • Hepatitis A Virus Cellular Receptor 1
  • Immunoglobulins
  • Ligands
  • Membrane Proteins
  • TIM-4 protein, mouse