Recombinant Ig-like transcript 3-Fc modulates T cell responses via induction of Th anergy and differentiation of CD8+ T suppressor cells

J Immunol. 2006 Mar 1;176(5):2790-8. doi: 10.4049/jimmunol.176.5.2790.


The Ig-like transcript (ILT)3 is crucial to the tolerogenic activity acquired by dendritic cells exposed to allospecific T suppressor (Ts) cells. We have explored the immunomodulatory property of the extracellular region of ILT3 using a cytoplasmic deletion mutant of ILT3 (ILT3delta), expressed as membrane-bound ILT3 on KG1 cells, and a rILT3-Fc fusion protein. We found that both membrane-bound and soluble ILT3 inhibited T cell proliferation in primary and secondary MLC inducing anergy in CD4+ Th cells and suppressing the differentiation of IFN-gamma-producing CD8+ CTL. Furthermore, membrane-bound and soluble ILT3 induced the differentiation of CD8+ FOXP3+ Ts cells in primary 7-day MLC. The suppressive activity of these CD8+ Ts cells is alloantigen specific and mediated by their capacity to induce the up-regulation of ILT3 and down-regulation of costimulatory molecules such as CD86 in APC from the stimulator used for priming, but not on control HLA-mismatched APC. Our finding that ILT3-Fc has potent immunosuppressive activity in vitro and that it acts on T cells only upon activation suggests the possibility that this agent may be of use for specific suppression of the immune response in autoimmunity or transplantation.

Publication types

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

MeSH terms

  • Cell Differentiation / immunology*
  • Cell Line
  • Clonal Anergy / immunology*
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Immunoglobulin Fc Fragments / physiology*
  • Membrane Glycoproteins
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / physiology*
  • Receptors, Immunologic
  • Recombinant Proteins / genetics
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Cytotoxic / cytology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism


  • Forkhead Transcription Factors
  • Immunoglobulin Fc Fragments
  • LILRB4 protein, human
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • Recombinant Proteins