Adam Krzystyniak1, Karolina Gołąb, Piotr Witkowski, Piotr Trzonkowski. 1. aDepartment of Clinical Immunology and Transplantology, Medical University of Gdańsk bIntercollegiate Faculty of Biotechnology University of Gdansk and Medical University of Gdansk, Gdańsk, Poland cDepartment of Surgery, Section of Transplantation, The University of Chicago, Chicago, Illinois, USA.
Abstract
PURPOSE OF REVIEW: T regulatory cells (Tregs) play a central role in maintaining immune homeostasis and peripheral tolerance to foreign antigens in humans. The immune response to alloantigens and recurrence of autoimmunity contribute to pancreatic islet transplant dysfunction, hence the adoptive transfer of Tregs has the potential to significantly improve islet graft survival. In this review, we provide an in-depth analysis of challenges associated with the application of ex-vivo expanded Tregs therapy in pancreatic islet transplant. RECENT FINDINGS: Tregs administered systemically may poorly migrate to the site of transplantation, which is critical for tolerance induction and graft protection. Intraportal administration of pancreatic tissue exerts some limitations on the ability to cotransplant Tregs at the same site of islet transplantation. In order to maximize therapeutic potential of Tregs, islet transplantation protocols may need additional refinement. Further to this, the Tregs may require cryopreservation in order to make them readily available at the same time as islet transplant. SUMMARY: On the basis of current experience and technology, the combination of islet and Treg cotransplantation is feasible and has great potential to improve islet graft survival. The possibility to wean off, or withdraw, traditional immunosuppressive agents and improve patient quality of life makes it an interesting avenue to be pursued.
PURPOSE OF REVIEW: T regulatory cells (Tregs) play a central role in maintaining immune homeostasis and peripheral tolerance to foreign antigens in humans. The immune response to alloantigens and recurrence of autoimmunity contribute to pancreatic islet transplant dysfunction, hence the adoptive transfer of Tregs has the potential to significantly improve islet graft survival. In this review, we provide an in-depth analysis of challenges associated with the application of ex-vivo expanded Tregs therapy in pancreatic islet transplant. RECENT FINDINGS:Tregs administered systemically may poorly migrate to the site of transplantation, which is critical for tolerance induction and graft protection. Intraportal administration of pancreatic tissue exerts some limitations on the ability to cotransplant Tregs at the same site of islet transplantation. In order to maximize therapeutic potential of Tregs, islet transplantation protocols may need additional refinement. Further to this, the Tregs may require cryopreservation in order to make them readily available at the same time as islet transplant. SUMMARY: On the basis of current experience and technology, the combination of islet and Treg cotransplantation is feasible and has great potential to improve islet graft survival. The possibility to wean off, or withdraw, traditional immunosuppressive agents and improve patient quality of life makes it an interesting avenue to be pursued.
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