Skip to main content

Interaction with activated monocytes enhances cytokine expression and suppressive activity of human CD4+CD45RO+CD25+CD127low regulatory T cells

Introduction

Despite the high frequency of CD4+ T cells with a regulatory phenotype (CD25+CD127lowFoxP3+) in the joints of patients with rheumatoid arthritis (RA), inflammation persists. Regulatory T cells (Tregs) can be converted into pro-inflammatory IL-17-producing cells by inflammatory mediators, particularly IL-1β.

Aim

To investigate whether activated monocytes, which are abundantly present in the rheumatic joint and potent producers of IL-1β, induce pro-inflammatory cytokine expression in Tregs and whether this impairs Treg function.

Materials and methods

The presence and phenotype of CD4+CD45RO+CD25+CD127low T cells (memory Tregs) and CD14+ monocytes in the peripheral blood (PB) and synovial fluid (SF) from patients with RA was investigated by flow cytometry. FACS-sorted memory Tregs from healthy controls were co-cultured with autologous in vitro-activated monocytes and anti-CD3 monoclonal antibody. Intracellular cytokine expression, phenotype and function were determined by flow cytometry, ELISA and proliferation assays.

Results

Patients with RA showed higher frequencies of CD4+CD45RO+CD25+CD127low Tregs and activated CD14+ monocytes in SF relative to PB. We demonstrate that activated monocytes induced an increase in the percentage of IL-17+, IFNγ+ and TNF-α+, but also IL-10+ Tregs. Blocking and reconstitution experiments revealed that the observed increase in IL-17+ and IFNγ+ Tregs was driven by monocyte-derived IL-1β, IL-6 and TNF-α and was mediated by both CD14+CD16- and CD14+CD16+ monocyte subsets. Despite enhanced cytokine expression, cells maintained their CD25+FoxP3+CD39+ Treg phenotype and showed enhanced capacity to suppress proliferation and IL-17 production by effector T cells.

Conclusion

Tregs exposed to a pro-inflammatory environment show increased suppressive activity.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Gina J Walter.

Rights and permissions

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and Permissions

About this article

Cite this article

Walter, G.J., Evans, H.G., Menon, B. et al. Interaction with activated monocytes enhances cytokine expression and suppressive activity of human CD4+CD45RO+CD25+CD127low regulatory T cells. J Transl Med 10, P3 (2012). https://doi.org/10.1186/1479-5876-10-S3-P3

Download citation

Keywords

  • Rheumatoid Arthritis
  • Flow Cytometry
  • Synovial Fluid
  • Cytokine Expression
  • Potent Producer