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Clin Immunol. 2017 Jan;174:1-9. doi: 10.1016/j.clim.2016.10.012. Epub 2016 Oct 29.

Intraperitoneal injection of IDO-expressing dermal fibroblasts improves the allograft survival.

Author information

1
Department of Surgery/Division of Plastic Surgery, University of British Columbia, Vancouver, BC, Canada.
2
Department of Surgery/Division of Plastic Surgery, University of British Columbia, Vancouver, BC, Canada. Electronic address: aghahary@mail.ubc.ca.

Abstract

Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme with tolerogenic effects on different immune cells. Our group has previously shown that co-transplantation of IDO-expressing fibroblasts with donor tissues can delay immune rejection by inducing local immunosuppression. In this study, we have employed a systemic approach to improve allograft survival without using any immunosuppressive medication. To achieve this, 10 million lentiviral transduced IDO-expressing donor derived fibroblasts were injected into the peritoneal cavity of allograft recipients. We showed that IDO-fibroblast therapy increases the survival of both islets and skin allografts and decreases the infiltration of immune cells in subcutaneous transplanted skins. Indirect pathway of allo-reactive T cell activation was suppressed more than the direct pathway. Injected IDO-fibroblasts were found in peritoneal cavity and mesenteric lymph nodes of the recipient mice. In conclusion, IDO-expressing fibroblast therapy proved to be a novel approach in improving the allogeneic graft survival.

KEYWORDS:

Allograft survival; Fibroblast; Indoleamine 2,3-dioxygenase

PMID:
27989895
DOI:
10.1016/j.clim.2016.10.012
[Indexed for MEDLINE]

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