Individuals with autoimmune type 1 diabetes, which is caused by immune cells known as T cells attacking the body's 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 body's 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 body's 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 accompanying commentary by Tom Van Belle and Matthias von Herrath, at the La Jolla Institute for Allergy and Immunology.
Journal reference: Islet transplantation in patients with autoimmune diabetes induces homeostatic cytokines that expand autoreactive memory T cells. Journal of Clinical Investigation. April 22, 2008.
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