TIM-4 expressed on APCs induces T cell expansion and survival

J Immunol. 2008 Apr 1;180(7):4706-13. doi: 10.4049/jimmunol.180.7.4706.

Abstract

TIM (T cell, Ig, mucin) proteins can regulate T cell immune responses. Tim-4 mRNA is not expressed in T cells, but exclusively in APCs. Tim-4 is a ligand for Tim-1 and Tim-4.Ig fusion protein was shown to either inhibit or expand T cells. However, the molecular basis for such opposite effects was not defined. By generating mAbs, we show that expression of Tim-4 protein is restricted to CD11c(+) and CD11b(+) cells and is up-regulated upon activation. We show that Tim-4 specifically phosphorylates Tim-1 and induces T cell expansion by enhancing cell division and reducing apoptosis. Tim-4 also induces the phosphorylation of signaling molecules LAT, Akt, and ERK1/2 in T cells. Tim-4, expressed on APCs, is a costimulatory molecule that promotes T cell expansion and survival by cross-linking Tim-1 on T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / metabolism*
  • Cell Differentiation / immunology*
  • Cell Line
  • Cell Survival / immunology
  • Cricetinae
  • Female
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism*
  • Mice
  • Rats
  • Signal Transduction / immunology
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Antibodies
  • Membrane Proteins
  • TIM-4 protein, mouse

Grants and funding