Research Group
- Dr. Anatolij Horuzsko, Principal Investigator
- Prof. Andrew Mellor, Co-Investigator
Location
- Medical College of Georgia, Augusta, USA
Title
- Prevention of Skin Allograft Rejection by HLA-G-Modified Dendritic Cells
A more complete understanding of natural immune mechanisms is needed to design better therapeutic approaches to achieve acceptance of transplanted tissues with minimal intervention by immunosuppressive drugs.
In vivo models of immune suppression are the most useful models for studies in transplantation because of their relevance to clinical transplantation in humans. The newly developed HLA-G transgenic mouse is an excellent model system for such studies. HLA-G is a human MHC class Ib molecule that is thought to regulate immune responses during pregnancy. We have generated HLA-G transgenic mice that express HLA-G in all major tissue. We found that the rejection of allogeneic skin grafts (donor skin from a different strain of mouse) is significantly delayed. In these mice dendritic cells were deficient in spontaneous maturation and induced T cell hyporesponsiveness. We found that this is due to the presence of HLA-G molecules. The HLA-G tetrameric complexes specifically bind a subset of myelomonocytic cells and inhibit maturation of dendritic cells in vitro. We propose that this binding occurs on murine cells via the receptor, a close homologue of the human inhibitory receptor, which is known to bind HLA-G. Determining the molecular mechanism and cellular process by which murine cells expressing HLA-G interfere with maturation of dendritic cells is the main focus of this study.
The proposed studies will help to establish a new approach to the processes that induce immune suppression. The results have the potential of providing new strategies for the management of transplants, allergy, autoimmune disease, resistance to infection and tumors, and immunodeficiency.
