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Immune Therapy following Pancreatic Islet Cell Transplant can Prevent Rejection

written by: Emma Lloyd • edited by: Leigh A. Zaykoski • updated: 12/29/2008

One potential treatment for type 1 diabetes is the transplant of human islet cells into a diabetic recipient. The problem then becomes how to keep the transplanted cells alive in the face of attack from the recipient’s immune system.

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    For people with type 1 diabetes, life is an endless cycle of balancing carbohydrates with exercise and insulin intake. The only way to eliminate this necessity is to receive a transplant of islet cells – the cells of the pancreas which make insulin.

    The problem with transplants is that the immune system is extremely inhospitable to strangers: that includes human strangers as well as bacteria and viruses – the immune system doesn’t recognize that a transplant of cells might be intended to be beneficial to the recipient, and won’t call off the attack just because the transplanted cells have come from another human.

    This is the basis of the problem of transplant immunology: the immune system, having evolved to recognize and destroy any biological matter of non-self origins, does not differentiate between human non-self and non-human non-self. All non-self is pretty much the same to the cells and molecules which make up the immune system.

    For this reason, anyone who receives a transplant – of islet cells or any other non-self cell type – must also take immunosuppressive drugs to prevent rejection of the transplant. Typically those drugs must be taken for as long as the transplant is in place, but there is yet another problem: these drugs put patients at risk of infection and even cancer, because they are non-specific drugs which dampen the entire immune system.

    There is a better solution to this approach, but as with all other types of transplants, it’s tricky. The solution is to trick the immune system into believing that the donor cells are self, rather than non-self.

    Researchers at Northwestern University's Feinberg School of Medicine believe they may have done exactly that in diabetic mice, by masking the non-self aspect of donor cells. To do this, they gave transplant recipients injections of donor antigen-presenting cells before and after transplanting islet cells. The cells were treated with a chemical called ethylene carbodiimide, a substance which is known to ‘mask’ the identity of cells and help to induce immunological tolerance to treated cells.

    This strategy worked amazingly well: more than 70% of recipient mice were able to maintain the donor cells in the long term, with tolerance to the grafted cells lasting 150 days. Without the injection of treated antigen-presenting cells, mice rejected the donor cells within 15 days.

    The next step, the researchers say, is to repeat this work in mice with an autoimmune disease that destroys islet cells, just as type 1 diabetes does. If this proves successful, human patients may be the next recipients of this experimental treatment. But there’s more – if the treatment works for one autoimmune disease, it may work for others, such as multiple sclerosis.

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    References

    Luo X, Pothoven KL, McCarthy D, DeGutes M, Martin A, Getts DR, Xia G, He J, Zhang X, Kaufman DB, Miller SD. ECDI-fixed allogeneic splenocytes induce donor-specific tolerance for long-term survival of islet transplants via two distinct mechanisms. Proc Natl Acad Sci U S A. 2008 Sep 23;105 (38):14527-32.