UCSF approach might end lifelong drug treatment.
Organ-transplant recipients often reject donated organs, but a new, two-pronged strategy developed by UC San Francisco researchers to specifically weaken immune responses that target transplanted tissue has shown promise in controlled experiments on mice.
The hope is that using this novel treatment strategy at the time of transplantation surgery could spare patients from lifelong immunosuppressive treatments and their side effects. The approach might also be used to treat autoimmune diseases such as type 1 diabetes, the researchers said. The study is published and commented upon in a recent issue of American Journal of Transplantation.
The study was conducted in mouse studies of islet-cell transplantation — a procedure used to restore insulin secretion and control over glucose levels in the blood in patients with life-threatening diabetes. The treatment allowed more than 70 percent of mice to accept transplants without requiring any long-term treatment with immunosuppressive drugs.
The approach, led by Diabetes Center member Qizhi Tang, Ph.D., involved using cells from donors to activate immune cells called donor-reactive effector T cells. The researchers then gave the mice a drug called cyclophosphamide, known to specifically kill activated cells.
Up to 80 percent of the donor-reactive effector T cells, which play a major role in transplant rejection, were eliminated by this treatment. However, that procedure alone did not prolong survival of transplanted tissue.
That required a second step: Some of the mice also received cell therapy — an expanded population of cells called TREGs that quell immune activity. Seventy percent to 80 percent of these mice accepted the transplants, without requiring any long-term immunosuppressive drugs.
Significantly, when the cell therapy was used only in those cells that specifically target donor tissue, only one-fifth as many cells were needed to prevent transplant rejection, the UCSF researchers found. The bigger bang per cell may bode well for clinical protocols, Tang suggested.