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This article is part of the supplement: 7th European Workshop on Immune-Mediated Inflammatory Diseases

Open Access Poster presentation

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

Gina J Walter1*, Hayley G Evans1, Bina Menon123, Bruce W Kirkham2, Andrew P Cope123, Frederic Geissmann1 and Leonie S Taams1

  • * Corresponding author: Gina J Walter

Author Affiliations

1 Centre for Molecular and Cellular Biology of Inflammation, King’s College London, London, UK

2 Dept. Rheumatology, Guy’s & St Thomas’ NHS Foundation Trust, London, UK

3 Academic Dept. Rheumatology, King’s College London, London, UK

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Journal of Translational Medicine 2012, 10(Suppl 3):P3  doi:10.1186/1479-5876-10-S3-P3


The electronic version of this article is the complete one and can be found online at: http://www.translational-medicine.com/content/10/S3/P3


Published:28 November 2012

© 2012 Walter et al; licensee 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.

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.