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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Diabetes Mellitus, Experimental / blood
  • Female
  • Fibroblasts / transplantation*
  • Graft Survival*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase*
  • Injections, Intraperitoneal
  • Islets of Langerhans Transplantation
  • Male
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Skin / cytology
  • Skin / immunology
  • T-Lymphocytes, Regulatory / immunology
  • Transplantation, Homologous

Substances

  • Blood Glucose
  • Indoleamine-Pyrrole 2,3,-Dioxygenase