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Short Report: CAR Tregs mediate linked suppression and infectious tolerance in islet transplantation.
- Source :
-
BioRxiv : the preprint server for biology [bioRxiv] 2024 Apr 10. Date of Electronic Publication: 2024 Apr 10. - Publication Year :
- 2024
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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 <superscript>+</superscript> 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 <superscript>+</superscript> 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-A2 <superscript>negative</superscript> 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.<br />Competing Interests: Competing interests: MKL holds patents and a license related to A2-CAR technology. All other authors declare that they have no competing interests.
Details
- Language :
- English
- Database :
- MEDLINE
- Journal :
- BioRxiv : the preprint server for biology
- Accession number :
- 38645184
- Full Text :
- https://doi.org/10.1101/2024.04.06.588414