Immunomodulation of Human CD19 + CD25 high Regulatory B Cells via Th17/Foxp3 Regulatory T Cells and Th1/Th2 Cytokines

Hum Immunol. 2019 Oct;80(10):863-870. doi: 10.1016/j.humimm.2019.05.011. Epub 2019 Jun 28.

Abstract

Regulatory B (Breg) cells are a special subset of immunoregulatory cells with unique phenotypes and functions. In this study, human CD19+CD25high Breg cells were purified from human peripheral blood. Based on the coculture system of Breg cells and CD4+ T cells in vitro, Breg cells were found to promote the increase in regulatory T (Treg) cells while decreasing the number of Th17 cells. Breg cells regulate Treg cells through two processes: cell-cell contact and cytokines. TGF-βsRII, a blocker of transforming growth factor-β (TGF-β), can attenuate the effects of Treg elevation, suggesting that TGF-β is the main cytokine, while Breg cells rather than interleukin-10 (IL-10) regulate the differentiation of Treg cells. However, Th17 cells were mainly regulated by cytokines, without an obvious regulatory effect on cell-cell contacts. Breg cells may regulate Th17 cells by a pathway independent of TGF-β and IL-6. The coculture of Breg cells and CD4+ T cells led to changes in the cytokine spectrum, which included significant increases in IL-4, IL-6 and IL-10 but not obvious changes in IL-2, IFN-γ and TNF. The inhibitory effect of Breg cells was weakened by blocking cell-cell contacts in cultures separated with the Transwell chamber because IL-10 decreased while IL-6 increased when compared with cocultured Breg and CD4+ T cells. When the IL-10 inhibitor IL-10sRα was added, IL-6 and TNF levels significantly increased, while treatment with the TGF-β inhibitor TGF-βsRII did not result in similar changes, suggesting that IL-10 is an important molecule to inhibit the proinflammatory factors IL-6 and TNF in this culture system.

Keywords: Cellular immunology; Human regulatory B.

MeSH terms

  • Adult
  • Antigens, CD19 / metabolism*
  • B-Lymphocytes, Regulatory / immunology*
  • Cell Differentiation / immunology
  • Cell Proliferation
  • Coculture Techniques / methods
  • Cytokines / metabolism
  • Female
  • Forkhead Transcription Factors / metabolism*
  • Healthy Volunteers
  • Humans
  • Interleukin-2 Receptor alpha Subunit / metabolism*
  • Male
  • T-Lymphocytes, Regulatory / immunology*
  • Th1-Th2 Balance*
  • Th17 Cells / immunology*

Substances

  • Antigens, CD19
  • CD19 molecule, human
  • Cytokines
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit