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

37 Citations (Scopus)

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
StatePublished - Apr 1 2007

Fingerprint

HLA-G Antigens
Dendritic Cells
Allografts
Transgenic Mice
T-Lymphocytes
Isoantigens
Regulatory T-Lymphocytes
Down-Regulation
Prospective Studies
Cytokines
Transplants
Skin
Research

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Mechanisms of Prolongation of Allograft Survival by HLA-G/ILT4-Modified Dendritic Cells. / Ristich, Vladimir; Zhang, Wei; Liang, Siyuan; Horuzsko, Anatolij.

In: Human Immunology, Vol. 68, No. 4, 01.04.2007, p. 264-271.

Research output: Contribution to journalArticle

Ristich, Vladimir ; Zhang, Wei ; Liang, Siyuan ; Horuzsko, Anatolij. / Mechanisms of Prolongation of Allograft Survival by HLA-G/ILT4-Modified Dendritic Cells. In: Human Immunology. 2007 ; Vol. 68, No. 4. pp. 264-271.
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