Genetic engineering of regulatory T cells for treatment of autoimmune disorders including type 1 diabetes

Tuomela, Karoliina; Levings, Megan K.

doi:10.1007/s00125-023-06076-2

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2024

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Cited by 5 publications

References 95 publications

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Approches vaccinales dans les maladies auto-immunes

Boitard

2024

Bulletin de l'Académie Nationale de Médecine

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Approches vaccinales dans les maladies auto-immunes

Boitard

2024

Bulletin de l'Académie Nationale de Médecine

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Regulatory T cell-based therapy in type 1 diabetes: Latest breakthroughs and evidence

Huang,

Zhu

2024

International Immunopharmacology

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CAR Tregs mediate linked suppression and infectious tolerance in islet transplantation

Wardell,

Fung,

Chen

et al. 2024

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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.

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Genetic engineering of regulatory T cells for treatment of autoimmune disorders including type 1 diabetes

Cited by 5 publications

References 95 publications

Approches vaccinales dans les maladies auto-immunes

Approches vaccinales dans les maladies auto-immunes

Regulatory T cell-based therapy in type 1 diabetes: Latest breakthroughs and evidence

CAR Tregs mediate linked suppression and infectious tolerance in islet transplantation

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