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Abatacept modulates proinflammatory macrophage responses upon cytokine-activated T cell and Toll-like receptor ligand stimulation
  1. M H Wenink1,
  2. K C M Santegoets1,
  3. A M Platt2,
  4. W B van den Berg1,
  5. P L C M van Riel1,
  6. P Garside2,
  7. T R D J Radstake1,
  8. I B McInnes2
  1. 1Department of Rheumatology, Nijmegen Center of Infection, Inflammation and Immunity (N4i) and Nijmegen Center for Molecular Life Science (NCMLS), Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  2. 2Division of Immunology, Infection and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, UK
  1. Correspondence to Dr T R D J Radstake, Department of Rheumatology, Nijmegen Center of Infection, Inflammation and Immunity (N4i) and Nijmegen Center for Molecular Life Science (NCMLS), Radboud University Nijmegen Medical Centre, Geert Grooteplein 8, 6500 HB Nijmegen, The Netherlands; t.radstake{at}reuma.umcn.nl

Abstract

Objectives We investigated whether Abatacept might reduce proinflammatory cytokine production by macrophages upon contact with cytokine activated T cells and/or stimulation with TLR ligands.

Methods Macrophages and cytokine stimulated T cells (Tck) were added together in the presence of Abatacept or a control Ig, with or without TLR ligands. The production of cytokines was determined by luminex.

Results Abatacept reduced Tck-induced production of TNFa by macrophages. Tck and TLR ligands synergistically induced the production of proinflammatory cytokines by macrophages, especially IL-12p70. The production of IL-12p70 coincided with the production of IFNg, which were both reduced in the presence of Abatacept.

Conclusions Tck induce the production of TNFa by macrophages and facilitate the highly increased production of proinflammatory cytokines in the presence of TLR ligands. Abatacept was shown to potently suppress these pathways suggesting that its role may extend beyond antigen specific T cell mediated effector function.

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Footnotes

  • Competing interests None.

  • Ethics approval The study was approved by the Radboud University Nijmegen Medical Centre medical ethics committee and the University of Glasgow medical ethics committee.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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