Research Group
- Dr. Michael D. Gunn, Principal Investigator
- Manabu Yanagita, Research Associate
Location
- Duke University Medical Center, Durham, USA
Title
- The Role of Plasmacytoid Dendritic Cells in the Development of Tolerance
It has long been thought that a population of antigen-presenting dendritic cells within the lymph nodes and spleen may act to inhibit immune responses by eliminating excessive or unwanted T lymphocytes. Such a function is required to eliminate self-reactive T lymphocytes and to terminate immune responses that have served their purpose. These cells may also be stimulated to eliminate T cells that mediate the rejection of organ transplants.
We have identified a mutation in mice that leads to excessive T cell responses, the decreased elimination of unwanted T cells, and a failure to develop transplant tolerance. This mutation involves genes that control cell migration and our studies suggest that this defect is due to the failure of a specific dendritic cell population to migrate into lymph nodes. In pursuing this defect, we have identified a novel dendritic cell type that may be involved in this process.
In these studies, we will use a model in which T cells are eliminated in normal mice but not in our mutant mice to identify the specific dendritic cell type that mediates the elimination of unwanted T cells. We will also examine the requirement for specific molecules that may be involved in this process and will examine the requirement for specific dendritic cell types in the development of transplantation tolerance.
This work should lead to a greater understanding of the mechanisms by which tolerance is initiated. In addition, the identification of a cell type that promotes the development of tolerance may have clinical applications.
