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The effects of anti–TNF agents on the expansion of T helper-type 17 cells driven by lipopolysaccharide-stimulated monocytes

  • Gianluca Fossati1,
  • Louise Healy1 and
  • Andrew Nesbitt1
Journal of Translational Medicine201210(Suppl 3):P42

https://doi.org/10.1186/1479-5876-10-S3-P42

Published: 28 November 2012

Keywords

Rheumatoid ArthritisInterferonTumor Necrosis FactorPeripheral Blood Mononuclear CellInfliximab

Introduction

T helper-type 17 (Th17) cells are proinflammatory CD4+ cells characterized by Interleukin-17 (IL-17) production. Evidence suggests cytokines produce by Th17s, including IL-17, are involved in rheumatoid arthritis (RA) pathogenesis [1]. Lipopolysaccharide (LPS)-stimulated monocytes promote CD4+ cell differentiation into Th17 cells, producing IL-17 in vitro[2].

Aim

Examine the effect of 4 anti–tumor necrosis factor (TNF) agents (adalimumab, etanercept, infliximab, and certolizumab pegol) on CD4+CD45RO+ memory T cell expansion into Th17 cells, driven by LPS-stimulated monocytes.

Patients and methods

Monocytes and CD4+ cells were purified, by positive and negative selection, from peripheral blood mononuclear cells of healthy volunteers. CD4+CD45RO+ memory T cells were enriched from the CD4+ cell fraction by positive selection. A 1:1 ratio of monocytes and memory T cells was co-cultured for 7 days with CD3/CD28 Human T-Activator Dynabeads and 1 μg/mL LPS. Cells were cultured with and without 10 μg/mL anti-TNF agent. Subsequently, CD4+ cells were stained for intracellular Interferon γ (INFγ) and IL-17A, and analyzed by flow cytometry. IL-17A and IL-17F secretion was determined by ELISA.

Results

IL-17A-producing CD4+ cell were 2.5-fold less frequent in co-cultures with the 4 anti-TNF agents compared to controls. IL-17A and IFNγ producing CD4+ cell levels were similar between the 4 anti-TNF agents. Compared to controls, IL-17A and IL-17F secretion into the supernatant was lower in anti-TNF exposed co-cultures (580 pg/mL vs. 180 pg/mL and 8 ng/mL vs. 2 ng/mL, respectively). There were no significant differences in the IL-17A or IL-17F concentration between co-cultures exposed to different anti-TNF agents.

Conclusion

Exposure to anti-TNF agents inhibited Th17 expansion and IL-17A production, suggesting that anti-TNF agents may reduce Th17 expansion and, as a consequence, IL-17A and IL-17F concentration.

Authors’ Affiliations

(1)
UCB Pharma, Slough, UK

References

  1. Pernis AB: Th17 cells in rheumatoid arthritis and systemic lupus erythematosus. J Intern Med. 2009, 265: 644-52. 10.1111/j.1365-2796.2009.02099.x.View ArticlePubMedGoogle Scholar
  2. Evans H: In vivo activated monocytes from the site of inflammation in humans specifically promote Th17 responses. Proc Natl Acad Sci U S A. 2009, 106: 6232-6237. 10.1073/pnas.0808144106.PubMed CentralView ArticlePubMedGoogle Scholar

Copyright

© Fossati et al; licensee BioMed Central Ltd. 2012

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.

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