Transplantation
Department of Medicine, Committee on Immunology, University of Chicago, Gwen Knapp Center for Lupus and Immunology Research, Chicago, IL 60637, USA.
Published: May 2012
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.
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http://dx.doi.org/10.1097/TP.0b013e31824d11d7 | DOI Listing |
Front Immunol
November 2024
Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL, United States.
Front Immunol
September 2024
Center of Critical Care Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
As an effective treatment for diabetes, islet transplantation has garnered significant attention and research in recent years. However, immune rejection and the toxicity of immunosuppressive drugs remain critical factors influencing the success of islet transplantation. While immunosuppressants are essential in reducing immune rejection reactions and can significantly improve the survival rate of islet transplants, improper use of these drugs can markedly increase mortality rates following transplantation.
View Article and Find Full Text PDFFront Immunol
September 2024
Center of Critical Care Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Front Immunol
September 2024
MetaLife Lab, Shenzhen Institute of Translational Medicine, Shenzhen, Guangdong, China.
Background: Islet transplantation is a promising treatment for type 1 diabetes that aims to restore insulin production and improve glucose control, but long-term graft survival remains a challenge due to immune rejection.
Methods: ScRNA-seq data from syngeneic and allogeneic islet transplantation grafts were obtained from GSE198865. Seurat was used for filtering and clustering, and UMAP was used for dimension reduction.
Clin Transplant
September 2024
Department of Renal Transplant Surgery, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India.
Introduction: Simultaneous pancreas-kidney transplantation (SPK) is the preferred treatment for individuals with type-1 diabetes and end-stage renal disease. However, a limited supply of "Ideal Pancreas Donors" contributed to a growing disparity between available organs and recipients. Even though SPK outcomes from pediatric donors match those from adult donors, unclear guidelines on minimum age and weight criteria for extra small pediatric pancreas donors lead to hesitancy among several transplant centers to utilize these grafts due to concerns about inadequate islet mass, technical challenges, and increased risk of allograft thrombosis.
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