Protection of islet grafts through transforming growth factor-beta-induced tolerogenic dendritic cells
Author(s)
Thomas, David C
Wong, F Susan
Zaccone, Paola
Green, E Allison
Wallberg, Maja
Type
Journal Article
Abstract
In type 1 diabetes, the insulin-producing β-cells are destroyed by the immune system. One way of restoring glucose control is to transplant β-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)-β within islets to achieve long-term graft tolerance. We found that brief expression of TGF-β 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-β 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-β–treated bone marrow–derived DCs to activate both CD4+ and CD8+ T cells was reduced. Adding TGF-β–conditioned tolerogenic DCs to the grafted islets led to long-term survival of the graft, demonstrating that TGF-β–induced tolerogenic DCs can provide an effective means to restore immune tolerance in an already established autoimmune disease.
Date Issued
2013-09-01
Date Acceptance
2013-05-24
Citation
Diabetes, 2013, 62 (9), pp.3132-3142
ISSN
0012-1797
Publisher
American Diabetes Association
Start Page
3132
End Page
3142
Journal / Book Title
Diabetes
Volume
62
Issue
9
Copyright Statement
© 2013 by the American Diabetes Association.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000323421000020&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
REGULATORY T-CELLS
COLLAGEN-INDUCED ARTHRITIS
TGF-BETA
NOD MICE
TRANSPLANT TOLERANCE
GENE-EXPRESSION
TRANSGENIC MICE
CUTTING EDGE
INDUCTION
TGF-BETA-1
Publication Status
Published
Date Publish Online
2013-08-22