CAR Tregs mediate linked suppression and infectious tolerance in islet transplantation
Wardell, C.; Fung, V.; Chen, E.; Haque, M.; Gillies, J.; Spanier, J.; Mojibian, M.; Fife, B. T.; Levings, M. K.
Show abstract
Regulatory T cells (Tregs) have potential as a cell-based therapy to prevent or treat transplant rejection and autoimmunity. Using an HLA-A2-specific chimeric antigen receptor (A2-CAR), we previously showed that adoptive transfer of A2-CAR Tregs limited anti-HLA-A2 alloimmunity. However, it was unknown if A2-CAR Tregs could also limit immunity to autoantigens. Using a model of HLA-A2+ islet transplantation into immunodeficient non-obese diabetic mice, we investigated if A2-CAR Tregs could control diabetes induced by islet-autoreactive (BDC2.5) T cells. In mice transplanted with HLA-A2+ islets, A2-CAR Tregs reduced BDC2.5 T cell engraftment, proliferation and cytokine production, and protected mice from diabetes. Tolerance to islets was systemic, including protection of the HLA-A2negative endogenous pancreas. In tolerant mice, a significant proportion of BDC2.5 T cells gained FOXP3 expression suggesting that long-term tolerance is maintained by de novo Treg generation. Thus, A2-CAR Tregs mediate linked suppression and infectious tolerance and have potential therapeutic use to simultaneously control both allo- and autoimmunity in islet transplantation. One Sentence SummaryAlloreactive chimeric antigen receptor-engineered regulatory T cells limit diabetogenic T cell engraftment and function to prevent type 1 diabetes.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Natural protection from type 1 diabetes in Non Obese Diabetic (NOD) mice is characterised by a unique pancreatic islet phenotype 95%
- Reduced function of the adaptor SH2B3 promotes T1D via altered γc cytokine-regulated, T cell intrinsic immune tolerance 95%
- Microvascular homeostasis is compromised in pancreatic islets in a mouse model of beta cell loss and low-grade inflammation 94%
Similar papers in this journal
Similar papers in this journal
- Inhibition of the Eukaryotic Initiation Factor-2-α Kinase PERK Decreases Risk of Autoimmune Diabetes in Mice 95%
- UTX coordinates TCF1 and STAT3 to control progenitor CD8+ T cell fate in autoimmune diabetes 94%
- Single cell transcriptomic analysis of renal allograft rejection reveals novel insights into intragraft TCR clonality 94%
Similar papers in this journal
- Regulation of layered T cell tolerance mechanisms by the NR4A family is essential to preserve immune homeostasis and suppress autoimmunity 94%
- Mitophagy protects beta cells from inflammatory damage in diabetes 94%
- Single-cell transcriptomics of allo-reactive CD4+ T cells over time reveals divergent fates during gut GVHD 94%
Similar papers in this journal
- Regulatory T cells suppress the formation of potent KLRK1 and IL-7R expressing effector CD8 T cells by limiting IL-2 95%
- Follicular helper- and peripheral helper-like T cells drive autoimmune disease in human immune system mice 94%
- Islet vascularization is regulated by primary endothelial cilia via VEGF-A dependent signaling 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.