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 language | English (US) |
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Pages (from-to) | 264-271 |
Number of pages | 8 |
Journal | Human Immunology |
Volume | 68 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2007 |
Keywords
- HLA-G
- allograft survival
- dendritic cells
- inhibitory receptors
- tolerance
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology