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Protection of Islet Grafts through transforming growth factor-β–induced Tolerogenic Dendritic cells

Thomas, D. C., Wong, F. Susan, Zaccone, P., Green, E. A. and Wallberg, M. 2013. Protection of Islet Grafts through transforming growth factor-β–induced Tolerogenic Dendritic cells. Diabetes 62 (9) , pp. 3132-3142. 10.2337/db12-1740

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Abstract

In type 1 diabetes, the insulin-producing b-cells are destroyed by the immune system. One way of restoring glucose control is to transplant b-cells from a donor. Although this procedure may restore endogenous insulin production, immunosuppressive treatment is needed to prevent the recipient from rejecting the donor-derived islets. We investigated the possibilities of transient expression of the immunosuppressive cytokine transforming growth factor (TGF)-b within islets to achieve long-term graft tolerance. We found that brief expression of TGF-b prevented rejection of syngeneic islets, that there was reduction of dendritic cell (DC) activation in the graft, and that there was reduced reactivation of T cells in the graft-draining lymph nodes. In vitro exposure of bone marrow–derived DCs to TGF-b reduced expression of costimulatory molecules CD80 and CD86, as well as production of proinflammatory cytokines such as interleukin-12 p70 in DCs, but did not alter levels of major histocompatibility complex classes I and II. Furthermore, the capacity of TGF-b–treated bone marrow–derived DCs to activate both CD4+ and CD8+ T cells was reduced. Adding TGF-b–conditioned tolerogenic DCs to the grafted islets led to long-term survival of the graft, demonstrating that TGF-b–induced tolerogenic DCs can provide an effective means to restore immune tolerance in an already established autoimmune disease.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: American Diabetes Association
ISSN: 0012-1797
Date of Acceptance: 24 May 2013
Last Modified: 09 Oct 2017 11:14
URI: http://orca.cf.ac.uk/id/eprint/105276

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