Mechanisms of prolongation of allograft survival by HLA-G/ILT4-modified dendritic cells.
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.
Ristich
Vladimir
V
Center for Molecular Chaperone/Radiobiology and Cancer Virology, Medical College of Georgia, Augusta, Georgia 30912, USA.
Zhang
Wei
W
Liang
Siyuan
S
Horuzsko
Anatolij
A
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000502:physiology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D016038:Skin Transplantation / Q000276:immunology*; D014184:Transplantation, Homologous
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; C491341:LILRB2 protein, human; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic