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AB0126 CD70 Expressing CD4 T Cells Produce IFN-Γ and IL-17 in Rheumatoid Arthritis
  1. J.K. Park1,
  2. B.K. Han2,
  3. J.A. Park1,
  4. Y.J. Woo1,
  5. S.Y. Kim1,
  6. E.Y. Lee1,
  7. E.B. Lee1,
  8. P. Chalan3,
  9. A.M. Boots3,
  10. Y.W. Song1
  1. 1Internal Medicine, Seoul National University Hospital, Seoul, Korea, Republic Of
  2. 2Internal Medicine, Cooper Medical School of Rowan University, New Jersey, United States
  3. 3Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, Groningen, Netherlands

Abstract

Background CD70 expressing CD4 T cells are enriched in rheumatoid arthritis (RA) and promote autoimmunity via costimulatory CD70-CD27 interaction. To date, it is unknown whether CD70+ CD4 T cells contribute to RA pathogenesis via other mechanisms than the CD70-CD27 interaction.

Objectives To explore the phenotype and cytokine production of CD70+ CD4 T cells in RA.

Methods Peripheral blood mononuclear cells (PBMCs) from 32 RA patients were isolated and frequencies of CD70+ cells within different CD4 T subsets were analyzed using flow cytometry. Interferon (IFN)-γ and interleukin (IL)-17 production were compared between the CD70+ and CD70- cells. Expression of master transcription factors T-bet, GATA3 and retinoic-acid-related orphan receptor gamma t (RORγt) were examined by real time-PCR. Results were in mean ± standard error of the mean.

Results CD4 T cells of healthy controls rarely expressed CD70 as compared to CD4 T cells of RA patients (0.9±0.3% vs. 7.6±0.6%, p<0.001, panel A). In RA, CD70+ cells were present within all CD4 T cell subsets, i.e. CD45RA+ CCR7+ naïve, CD45RA-CCR7+ central memory, CD45RA-CCR7- effector memory, and CD45RA+ CCR7- terminally differentiated effector memory T cells with a frequency of 3.9±1.1%, 4.0±0.5%, 4.2±0.7%, and 9.4±4.3%, respectively (panel B). As compared to CD70- CD4 T cells, CD70+ CD4 T cells produced significantly more IFN-γ (panel C) and IL-17 (panel D) after short activation. CD70+ CD4 T cells preferentially expressed transcription factor RORγt.

Conclusions CD70+ CD4 T cells are enriched in RA and may directly contribute to RA pathogenesis by producing IFN-γ and IL-17. Targeting CD70+ CD4 T cells might offer new therapeutic opportunities in RA.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.2780

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