2025/01/20 by Peter J. Eggenhuizen, Boaz H. Ng, Cecilia Lo +8 · 1 voice
Immunology and Microbiology · Medicine · #T-cell and B-cell Immunology #Renal Diseases and Glomerulopathies #Phagocytosis and Immune Regulation
paper · pdf · doi:10.1016/j.kint.2025.01.005
openalex publication_date 2025/01/20 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
Anti–glomerular basement membrane (anti-GBM) disease is accompanied by insufficient antigen-specific regulatory T cells (Tregs) and clonally expanded antigen-specific conventional T cells. In particular, this applied to the immunodominant T cell autoepitope of type IV collagen, α3(IV)NC1 135–145 , presented by human leukocyte antigen–DRB1∗1501. Here, we investigated whether Tregs engineered to express GBM–T cell receptors (TCR) specific for α3(IV)NC1 135–145 better suppress autoimmunity. The GBM-TCR Treg cell product exhibited a phenotypically stable Treg phenotype, produced α3(IV)NC1 135–145 –specific functional responses, and were superior suppressors of autoreactive conventional T cells and bystander conventional T cells compared to polyclonal Tregs or irrelevant TCR-transduced Tregs. We also found that GBM-TCR Tregs modulate other immune cells like dendritic cells and B cells to a more tolerogenic phenotype. Importantly, our findings support the development of GBM-TCR Tregs as a promising cell-based therapy for anti-GBM disease.