Mechanisms of Prolongation of Allograft Survival by HLA-G/ILT4-Modified Dendritic Cells

Vladimir Ristich, Wei Zhang, Siyuan Liang, Anatolij Horuzsko

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Engagement of inhibitory receptors on dendritic cells (DCs) is a powerful way to modulate their functions to achieve hyporesponsiveness or tolerance induction. Transgenic mice expressing human ILT4 receptor exclusively on DCs and triggered by HLA-G1 developed long-term survival of allogeneic skin transplant. Here we identify the cellular and molecular mechanisms responsible for that induction of hyporesponsiveness to alloantigen in vivo. Engagement of ILT4 receptor by HLA-G1 resulted in down-regulation of expression of MHC class II and costimulatory molecules, and modulation of cytokine production on DCs. HLA-G-modified DCs from ILT4 transgenic mice promote long-term survival of allografts by mechanisms involving both the induction of regulatory T cells and T-cell anergy. A novel feature of our research was to establish a model for the study of the prospective mechanisms of regulation of alloimmune responses by inhibitory receptors in vivo and analysis of the potential of HLA-G and its inhibitory receptors in modulation of DCs and T-cell function.

Original languageEnglish (US)
Pages (from-to)264-271
Number of pages8
JournalHuman Immunology
Volume68
Issue number4
DOIs
Publication statusPublished - Apr 1 2007

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Keywords

  • HLA-G
  • allograft survival
  • dendritic cells
  • inhibitory receptors
  • tolerance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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