Role of T-cell-specific nuclear factor κB in islet allograft rejection

Transplantation. 2012 May 27;93(10):976-82. doi: 10.1097/TP.0b013e31824d11d7.


Background: Pancreatic islet transplantation has the potential to cure type 1 diabetes, a chronic lifelong disease, but its clinical applicability is limited by allograft rejection. Nuclear factor κB (NF-κB) is a transcription factor important for survival and differentiation of T cells. In this study, we tested whether NF-κB in T cells is required for the rejection of islet allografts.

Methods: Mice expressing a superrepressor form of NF-κB selectively in T cells (IκBαΔN-Tg mice) with or without the antiapoptotic factor Bcl-xL, or mice with impaired T-cell receptor (TCR)- and B cell receptor-driven NF-κB activity (CARMA1-KO mice) were rendered diabetic and transplanted with islet allografts. Secondary skin transplantation in long-term acceptors of islet allografts was used to test for the development of donor-specific tolerance. Immune infiltration of the transplanted islets was examined by immunofluorescence. TCR-transgenic CD4 T cells were used to follow T-cell priming and differentiation.

Results: Islet allograft survival was prolonged in IκBαΔN-Tg mice, although the animals did not develop donor-specific tolerance. Reduced NF-κB activity did not prevent T-cell priming or differentiation but reduced survival of activated T cells, as transgenic expression of Bcl-xL restored islet allograft rejection in IκBαΔN-Tg mice. Abolishing TCR- and B cell receptor-driven activation of NF-κB selectively by CARMA1 deficiency prevented T-cell priming and islet allograft rejection.

Conclusions: Our data suggest that T cell-NF-κB plays an important role in the rejection of islet allografts. Targeting NF-κB selectively in lymphocytes seems a promising approach to facilitate acceptance of transplanted islets.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CARD Signaling Adaptor Proteins / physiology
  • Graft Rejection / etiology*
  • Graft Survival
  • Immune Tolerance
  • Islets of Langerhans Transplantation / immunology*
  • Isoantigens / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / physiology*
  • T-Lymphocytes / immunology*
  • Transplantation, Homologous


  • CARD Signaling Adaptor Proteins
  • Card11 protein, mouse
  • Isoantigens
  • NF-kappa B