| First Author | Thomas DC | Year | 2013 |
| Journal | Diabetes | Volume | 62 |
| Issue | 9 | Pages | 3132-42 |
| PubMed ID | 23715623 | Mgi Jnum | J:208957 |
| Mgi Id | MGI:5565432 | Doi | 10.2337/db12-1740 |
| Citation | Thomas DC, et al. (2013) Protection of islet grafts through transforming growth factor-beta-induced tolerogenic dendritic cells. Diabetes 62(9):3132-42 |
| abstractText | In type 1 diabetes, the insulin-producing beta-cells are destroyed by the immune system. One way of restoring glucose control is to transplant beta-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)-beta within islets to achieve long-term graft tolerance. We found that brief expression of TGF-beta 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-beta 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-beta-treated bone marrow-derived DCs to activate both CD4(+) and CD8(+) T cells was reduced. Adding TGF-beta-conditioned tolerogenic DCs to the grafted islets led to long-term survival of the graft, demonstrating that TGF-beta-induced tolerogenic DCs can provide an effective means to restore immune tolerance in an already established autoimmune disease. |
