Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 43, Issue 3, Pages 734-746Publisher
WILEY-BLACKWELL
DOI: 10.1002/eji.201242914
Keywords
Corneal transplantation; Dendritic cells; Gene therapy; Tolerance induction; Transplantation tolerance
Categories
Funding
- Roche Organ Transplantation Research Foundation (ROTRF)
- Wellcome Trust
- British Heart Foundation
- British Heart Foundation [PG/09/085/27949, RG/08/005/25303] Funding Source: researchfish
- Medical Research Council [MR/J006742/1] Funding Source: researchfish
Ask authors/readers for more resources
Dendritic cell (DC) modification is a potential strategy to induce clinical transplantation tolerance. We compared two DC modification strategies to inhibit allogeneic T-cell proliferation. In the first strategy, murine DCs were transduced with a lentiviral vector expressing CTLA4-KDEL, a fusion protein that prevents surface CD80/86 expression by retaining the co-stimulatory molecules within the ER. In the second approach, DCs were transduced to express the tryptophan-catabolising enzyme IDO. CTLA4-KDEL-expressing DCs induced anergy in alloreactive T cells and generated both CD4+CD25+ and CD4+CD25 Treg cells (with direct and indirect donor allospecificity and capacity for linked suppression) both in vitro and in vivo. In contrast, T-cell unresponsiveness induced by IDO+ DCs lacked donor specificity. In the absence of any immunosuppressive treatment, i.v. administration of CTLA4-KDEL-expressing DCs resulted in long-term survival of corneal allografts only when the DCs were capable of indirect presentation of alloantigen. This study demonstrates the therapeutic potential of CTLA4-KDEL-expressing DCs in tolerance induction.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available