Inducing Transplant Tolerance via Multiple Pathways

These researchers previously showed that giving special, chemically-treated white blood cells from the spleen before an islet transplant allows indefinite survival of the transplanted islets in an animal model without the need for any immunosuppression. How this regimen protects the transplanted islets is unclear. In this study, they showed that the infused chemically-treated white blood cells from the spleen differentially target certain T cells causing their rapid depletion. Other T cells are sequestered in the spleen preventing their attack on the transplanted islets and another type of regulatory T cell is induced at the site of the graft. It was concluded that these special infusions target host immune responses via a multitude of mechanisms, including T cell depletion, induction of tolerance to islets, and immune regulation, which act in a synergistic fashion to induce robust transplant tolerance. This simple form of immune tolerance induction has significant potential for clinical translation in human transplantation and in the context of JDRFs beta cell regeneration program.

Reference:

Ethylenecarbodiimide-fixed donor splenocyte infusions differentially target direct and indirect pathways of allorecognition for induction of transplant tolerance. J Immunol. 2012 Jul 15;189(2):804-12.

Investigators and Institutions:

The study was led by Dr. Luo and her colleagues at Northwestern University.

Ramifications for Individuals with Type 1 Diabetes:

Islet transplantation has been shown to have great efficacy in T1D individuals; making many people with T1D insulin independent for at least a period of time and impacting hypoglycemia unawareness. One of the limiting factors is the use of chronic immunosuppression (the other is the limited supply of human islets). This research is a promising approach to remove or reduce the need for chronic immunosuppression following human islet transplantation. It may also prove valuable in various encapsulation products and regeneration strategies.

JDRF Involvement:

This study was funded in part by JDRF grants to Dr. Luos laboratory.