High-affinity chimeric antigen receptor signaling induces an inflammatory program in human regulatory T cells.

ABSTRACT: Regulatory T cells (Tregs) are promising cellular therapies to induce immune tolerance in organ transplantation and autoimmune disease. The success of chimeric antigen receptor (CAR) T cell therapy for cancer has sparked interest in using CARs to generate antigen-specific Tregs. Here, we compared CAR with endogenous T cell receptor (TCR)/CD28 activation in human Tregs. Strikingly, CAR Tregs displayed increased cytotoxicity and diminished suppression of antigen-presenting cells and effector T (Teff) cells compared with TCR/CD28-activated Tregs. RNA sequencing revealed that CAR Tregs activate Teff cell gene programs. Indeed, CAR Tregs secreted high levels of inflammatory cytokines, with a subset of FOXP3⁺ CAR Tregs uniquely acquiring CD40L surface expression and producing IFN-γ. I

SUBMITTER: Cochrane RW 

PROVIDER: S-EPMC11647616 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature