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JCI table of contents: April 22, 2008
Date:4/22/2008

N: One reason why curative transplants might fail in type 1 diabetics

Individuals with autoimmune type 1 diabetes, which is caused by immune cells known as T cells attacking the bodys own insulin-producing pancreatic islet cells, need daily injections with insulin to control their blood sugar levels. This dependence on insulin injections can be circumvented by transplantation with islet cells. However, transplant recipients must be treated with a drug regimen, known as the Edmonton protocol, that decreases their number of T cells in an attempt to prevent the transplanted islet cells from being attacked by T cells that recognize the new islet cells as being from another human and from the same T cells that attacked the bodys original islet cells. Despite the drug regimen, islet cell transplants eventually fail in most recipients. New data, generated by Ezio Bonifacio and colleagues, at Dresden University of Technology, Germany, have indicated that the T cells that attacked the bodys original islet cells increase in number following treatment with the Edmonton protocol, leading them to suggest that this contributes to transplant failure.

In the study, the T cell loss caused by the Edmonton protocol was shown to be associated with the production of soluble factors that stimulate T cell proliferation as well as an increase in the number of T cells that recognize a protein (GAD65) expressed by islet cells. In two transplant recipients studied, two of the drugs in the Edmonton protocol (FK506 and rapamycin) were replaced with an alternative (micophenolate mofetil). No increase in the number of T cells that recognize GAD65 was observed in these individuals, leading the authors to suggest that drug regimens that do not promote the expansion of T cells might improve the outcome of islet cell transplantation. The importance of these observations for the ongoing development of new protocols for ensuring islet cell transplant survival is discussed in an a
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Journal of Clinical Investigation
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