CD19-targeted CAR regulatory T cells suppress B cell pathology without GvHD.

JCI Insight
Yuki ImuraAkihiko Yoshimura

Abstract

Regulatory T cells (Tregs) play essential roles in maintaining immunological self-tolerance and preventing autoimmunity. The adoptive transfer of antigen-specific Tregs has been expected to be a potent therapeutic method for autoimmune diseases, severe allergy, and rejection in organ transplantation. However, effective Treg therapy has not yet been established because of the difficulty in preparing a limited number of antigen-specific Tregs. Chimeric antigen receptor (CAR) T cells have been shown to be a powerful therapeutic method for treating B cell lymphomas, but application of CAR to Treg-mediated therapy has not yet been established. Here, we generated CD19-targeted CAR (CD19-CAR) Tregs from human PBMCs (hPBMCs) and optimized the fraction of the Treg source as CD4+CD25+CD127loCD45RA+CD45RO-. CD19-CAR Tregs could be expanded in vitro while maintaining Treg properties, including high expression of the latent form of TGF-β. CD19-CAR Tregs suppressed IgG antibody production and differentiation of B cells via a TGF-β-dependent mechanism. Unlike conventional CD19-CAR CD8+ T cells, CD19-CAR Tregs suppressed antibody production in immunodeficient mice that were reconstituted with hPBMCs, reducing the risk of graft-versus-host dise...Continue Reading

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Citations

Sep 13, 2020·Cellular & Molecular Immunology·Ryota SakaiAkihiko Yoshimura
Jan 28, 2021·Cancers·Vicky Mengfei QinJoe Jiang Zhu
Jan 25, 2021·International Immunopharmacology·Qianqian YuWei Wei
Dec 31, 2020·International Journal of Molecular Sciences·Demetra S M ChatzileontiadouEmma J Grant
Aug 21, 2021·Current Opinion in Biotechnology·Gianna T FlintJulian N Rosenberg
Jan 29, 2022·Expert Opinion on Biological Therapy·Marko RadicTony Marion

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Methods Mentioned

BETA
transgenic
FACS
density gradient centrifugation
PCR
flow cytometry
ELISA
PMA

Software Mentioned

GraphPad Prism
Diva
GraphPad
FlowJo

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