Regulatory dendritic cells for promotion of liver transplant operational tolerance: Rationale for a clinical trial and accompanying mechanistic studies

Hum Immunol. 2018 May;79(5):314-321. doi: 10.1016/j.humimm.2017.10.017. Epub 2017 Oct 31.


Dendritic cells (DC) are rare, bone marrow (BM)-derived innate immune cells that critically maintain self-tolerance in the healthy steady-state. Regulatory DC (DCreg) with capacity to suppress allograft rejection and promote transplant tolerance in pre-clinical models can readily be generated from BM precursors or circulating blood monocytes. These DCreg enhance allograft survival via various mechanisms, including promotion of regulatory T cells. In non-human primates receiving minimal immunosuppressive drug therapy (IS), infusion of DCreg of donor origin, one week before transplant, safely prolongs renal allograft survival and selectively attenuates anti-donor CD8+ memory T cell responses in the early post-transplant period. Based on these observations, and in view of the critical need to reduce patient dependence on non-specific IS agents that predispose to cardiometabolic side effects and renal insufficiency, we will conduct a first-in-human safety and preliminary efficacy study of donor-derived DCreg infusion to achieve early (18 months post-transplant) complete IS withdrawal in low-risk, living donor liver transplant recipients receiving standard-of-care IS (mycophenolate mofetil, tacrolimus and steroids). We will test the hypothesis that, although donor-derived DCreg are short-lived, they will induce robust donor-specific T cell hyporesponsiveness. We will examine immunological mechanisms by sequential analysis of blood and tissue samples, incorporating cutting-edge technologies.

Keywords: Cell therapy; Dendritic cells; Liver transplantation; Tolerance.

Publication types

  • Review

MeSH terms

  • Animals
  • Dendritic Cells / immunology
  • Dendritic Cells / transplantation*
  • Graft Rejection / immunology
  • Graft Survival / immunology
  • Humans
  • Immunologic Memory / immunology
  • Kidney Transplantation
  • Liver Transplantation
  • Models, Animal
  • T-Lymphocytes, Regulatory / immunology
  • Transplantation Tolerance / immunology*