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Tregs with an MHC class II peptide-specific chimeric antigen receptor prevent autoimmune diabetes in mice
- Source :
- Journal of Clinical Investigation. September 15, 2023, Vol. 133 Issue 18, p1, 13 p.
- Publication Year :
- 2023
-
Abstract
- Adoptive immunotherapy with Tregs is a promising approach for preventing or treating type 1 diabetes. Islet Antigen-specific Tregs have more potent therapeutic effects than polyclonal cells, but their low frequency is a barrier for clinical application. To generate Tregs that recognize islet antigens, we engineered a chimeric antigen receptor (CAR) derived from a monoclonal antibody with specificity for the insulin B chain 10-23 peptide presented in the context of the I[A.sup.g7] MHC class II allele present in NOD mice. Peptide specificity of the resulting InsB-g7 CAR was confirmed by tetramer staining and T cell proliferation in response to recombinant or islet-derived peptide. The InsB-g7 CAR redirected NOD Treg specificity such that insulin B 10-23-peptide stimulation enhanced suppressive function, measured via reduction of proliferation and IL-2 production by BDC2.5 T cells and CD80 and CD86 expression on dendritic cells. Cotransfer of InsB-g7 CAR Tregs prevented adoptive transfer diabetes by BDC2.5 T cells in immunodeficient NOD mice. In WT NOD mice, InsB-g7 CAR Tregs prevented spontaneous diabetes. These results show that engineering Treg specificity for islet antigens using a T cell receptor-like CAR is a promising therapeutic approach for the prevention of autoimmune diabetes.<br />Introduction Autoimmune type 1 diabetes (T1D) is caused by T cell-mediated destruction of the insulin-producing [beta] cells of the islets of Langerhans in the pancreas. Tregs, defined by expression of [...]
- Subjects :
- Thermo Fisher Scientific Inc.
STEMCELL Technologies Inc.
Scientific equipment and supplies industry -- Health aspects
T cells -- Health aspects
Type 1 diabetes -- Health aspects
Antigens -- Health aspects
Dendritic cells -- Health aspects
Diagnostic reagents industry -- Health aspects
Monoclonal antibodies -- Health aspects
Peptides -- Health aspects
Health care industry
Subjects
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 133
- Issue :
- 18
- Database :
- Gale General OneFile
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.768824529
- Full Text :
- https://doi.org/10.1172/JCI168601