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

Yuki Imura, Makoto Ando, Taisuke Kondo, Minako Ito, Akihiko Yoshimura

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)


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 disease. Therefore, the adoptive transfer of CD19-CAR Tregs may provide a novel therapeutic method for treating autoantibody-mediated autoimmune diseases.

Original languageEnglish
Article numbere136185
JournalJCI Insight
Issue number14
Publication statusPublished - Jun 23 2020

All Science Journal Classification (ASJC) codes

  • General Medicine


Dive into the research topics of 'CD19-targeted CAR regulatory T cells suppress B cell pathology without GvHD'. Together they form a unique fingerprint.

Cite this