Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4

Nat Immunol. 2002 Mar;3(3):237-43. doi: 10.1038/ni760. Epub 2002 Jan 28.


Immunoglobulin-like transcript 3 (ILT3) and ILT4 belong to a family of inhibitory receptors expressed by human monocytes and dendritic cells. We show here that CD8+CD28(-) alloantigen-specific T suppressor (TS) cells induce the up-regulation of ILT3 and ILT4 on monocytes and dendritic cells, rendering these antigen-presenting cells (APCs) tolerogenic. Tolerogenic APCs show reduced expression of costimulatory molecules and induce antigen-specific unresponsiveness in CD4+ T helper cells. Studies of human heart transplant recipients showed that rejection-free patients have circulating TS cells, which induce the up-regulation of ILT3 and ILT4 in donor APCs. These findings demonstrate an important mechanism of immune regulation.

Publication types

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

MeSH terms

  • Antigen-Presenting Cells / chemistry
  • Antigen-Presenting Cells / physiology
  • CD28 Antigens / analysis
  • CD8 Antigens / analysis
  • Dendritic Cells / physiology*
  • Humans
  • Immune Tolerance*
  • Membrane Glycoproteins
  • NF-kappa B / physiology
  • Receptors, Cell Surface / physiology*
  • Receptors, Immunologic / physiology*
  • T-Lymphocytes, Regulatory / immunology*


  • CD28 Antigens
  • CD8 Antigens
  • LILRB2 protein, human
  • LILRB4 protein, human
  • Membrane Glycoproteins
  • NF-kappa B
  • Receptors, Cell Surface
  • Receptors, Immunologic