Year 2 + NCE (new end 12/31/12)
We have recently identified therapeutic populations of white blood cells, called dendritic cells that can inhibit the development of immune rejection responses to foreign grafts, such as stem cells used in regenerative medicine. Dendritic cells usually act as messenger cells that traffic from tissues to regional lymph nodes to initiate potent adaptive immune responses to foreign grafts or invading pathogens for example. We however, have characterized populations of “messenger” dendritic cells that can shut off immune responses by generating potent adaptive immune suppressor cells. We have isolated these dendritic cells based on their expression of trafficking or adhesion molecules on the cell surface that target them to unique sites in the body where autoaggressive immune cells are either killed off or shut down during the development of the immune system. The use of such cell-surface molecules as markers are invaluable to isolate large numbers of dendritic cell subsets for use in cellular adoptive immunotherapy.
In addition, we have also used our recently characterized immunosuppressive dendritic cells as facilitator cells in transplants of bone marrow stem cells from a foreign donor. The idea behind this approach is that donor immunosuppressive dendritic cells will educate the immune system in the recipient to recognize cells and proteins derived from the donor as “self” and therefore not to mount destructive rejection responses to stem cell grafts that are to be infused from the same donor. We are currently working on establishing protocols for the use of immunosuppressive dendritic cells as facilitator cells for foreign stem cell grafts in the clinic.