A Comparison of Ex Vivo Expanded Human Regulatory T Cells Using Allogeneic Stimulated B Cells or Monocyte-Derived Dendritic Cells

Linda M. Lee, Hong Zhang, Karim Lee, Horace Liang, Alexander Merleev, Flavio Vincenti, Emanual Maverakis, Angus W. Thomson, Qizhi Tang

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Alloreactive regulatory T cells (arTregs) are more potent than polyclonal Tregs at suppressing immune responses to transplant antigens. Human arTregs can be expanded with allogeneic CD40L-stimulated B cells (sBcs) or stimulated-matured monocyte-derived dendritic cells (sDCs). Here, we compared the expansion efficiency and properties of arTregs stimulated ex vivo using these two types of antigen-presenting cells. Compared to sBcs, sDCs stimulated Tregs to expand two times more in number. The superior expansion-inducing capacity of sDCs correlated with their higher expression of CD80, CD86, and T cell-attracting chemokines. sBc- and sDC-arTregs expressed comparable levels of FOXP3, HELIOS, CD25, CD27, and CD62L, demethylated FOXP3 enhancer and in vitro suppressive function. sBc- and sDCs-arTregs had similar gene expression profiles that were distinct from primary Tregs. sBc- and sDC-arTregs exhibited similar low frequencies of IFN-γ, IL-4, and IL-17A-producing cells, and the cytokine-producing arTregs expressed high levels of FOXP3. Almost all sBc- and sDC-arTregs expressed CXCR3, which may enable them traffic to inflammatory sites. Thus, sDCs-arTregs that expand more readily, are phenotypically similar to sBc-arTregs, supporting sDCs as a viable alternative for arTreg production for clinical evaluation.

Original languageEnglish (US)
Article number679675
JournalFrontiers in immunology
Volume12
DOIs
StatePublished - Jun 18 2021

Keywords

  • B cells
  • dendritic cells
  • human
  • immune regulation
  • regulatory T cell
  • transplant tolerance
  • transplantation
  • Treg therapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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