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Preferential type 1 chemokine receptors and cytokine production of CD28 T cells in ankylosing spondylitis
  1. C Duftner1,
  2. C Dejaco1,
  3. W Kullich3,
  4. A Klauser2,
  5. C Goldberger1,
  6. A Falkenbach4,
  7. M Schirmer1
  1. 1Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria
  2. 2Department of Radiology, Innsbruck Medical University, Innsbruck, Austria
  3. 3Ludwig-Boltzmann Institute, Saalfelden, Austria
  4. 4Rehabilitationszentrum-Sonderkrankenanstalt Bad-Ischl der Pensionsversicherungsanstalt, Bad Ischl, Austria
  1. Correspondence to:
    Associate Professor M Schirmer
    Department of Internal Medicine, Innsbruck Medical University, A-6020 Innsbruck, Anichstrasse 35, Austria; michael.schirmer{at}uibk.ac.at

Abstract

Objective: To examine serum levels of type 1 and type 2 chemokines and lymphocytic expression of chemokine receptors, and to compare the results with lymphocytic cytokine production in patients with ankylosing spondylitis (AS).

Methods: Twelve patients with AS (mean (SD) age 44.9 (14.7) years) and 27 healthy controls (46.4 (12.8) years) were enrolled into the study. The expression of chemokine receptors (CCR-5, CXCR-3, CCR-4) and cytokines (interferon γ (IFNγ), interleukin (IL)2, IL4, IL10, tumour necrosis factor α (TNFα)) on CD28+ and CD28 T cell subtypes was analysed by a three colour FACS technique of peripheral blood samples. Serum ELISAs were performed to detect the CCR-5 ligands CCL-5, CCL-3; the CXCR-3 ligands CXCL-10, CXCL-9; and the CCR-4 ligand, CCL-17 before and after administration of the TNFα blocking agent infliximab.

Results: CD4+CD28 T cells had higher ratios of CXCR-3 to CCR-4 than CD4+CD28+ T cells. Both, CD4+ and CD8+CD28 T cells of patients with AS produced more IFNγ, TNFα, and IL10 than their CD28+ counterparts (p<0.05), and lacked the production of IL2 and IL4. Serum levels of CXCL-9 were increased in patients with AS to 59.2 pg/ml (34.1–730.5) compared with 32.5 pg/ml (20.0–79.5) in healthy controls (p = 0.016). The levels of both type 1 (CCL-5, CXCL-9) and type 2 chemokines (CCL-17) decreased under blockade of TNFα (p<0.05).

Conclusions: The profile of chemokine receptor expression and cytokine production by CD28 T cells suggests a type 1 immune reaction in AS, although IL10 is frequently produced by CD28 T cells. Treatment with TNFα blocking antibodies decreased both types of chemokines in patients’ sera.

  • AS, ankylosing spondylitis
  • BASDAI, Bath Ankylosing Disease Activity Index
  • BASFI, Bath Ankylosing Spondylitis Functional Index
  • BASMI, Bath Ankylosing Spondylitis Metrology Index
  • CRP, C reactive protein
  • ESR, erythrocyte sedimentation rate
  • IFNγ, interferon γ
  • IL, interleukin
  • PBMCs, peripheral blood mononuclear cells
  • PMA, phorbol 12-myristate 13-acetate
  • RA, rheumatoid arthritis
  • SpA, spondyloarthritis
  • TNFα, tumour necrosis factor α
  • ankylosing spondylitis
  • chemokines
  • chemokine receptors
  • cytokines
  • tumour necrosis factor α

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Footnotes

  • Published Online First 11 October 2005

  • Competing interests: None.

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