Expression of the inflammatory chemokines CCL5, CCL3 and CXCL10 in juvenile idiopathic arthritis, and demonstration of CCL5 production by an atypical subset of CD8+ T cells

doi:10.1186/ar1913

Arthritis Research & Therapy

Volume 8
Issue 2

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Pharoah DS
Varsani H
Tatham RW
Newton KR
de Jager W
Prakken BJ
Klein N
Wedderburn LR

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Pharoah DS
Varsani H
Tatham RW
Newton KR
de Jager W
Prakken BJ
Klein N
Wedderburn LR
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Research article

Expression of the inflammatory chemokines CCL5, CCL3 and CXCL10 in juvenile idiopathic arthritis, and demonstration of CCL5 production by an atypical subset of CD8+ T cells

Daniel S Pharoah¹ , Hemlata Varsani¹ , Richard W Tatham¹ , Katy R Newton¹ , Wilco de Jager² , Berent J Prakken² , Nigel Klein³ and Lucy R Wedderburn¹

¹Rheumatology Unit, Institute of Child Health, UCL, London, UK

²Department of Paediatric Immunology, Wilhelmina Children's Hospital, University Medical Centre, Utrecht

³Microbiology/Infectious Disease Unit, Institute of Child Health, UCL, London, UK

author email corresponding author email

Arthritis Research & Therapy 2006, 8:R50doi:10.1186/ar1913


Published:	28 February 2006

Abstract

This study focuses upon three chemokines, namely CCL5, CXCL10 and CCL3, which are potential novel therapeutic targets in arthritis. The aim of the study was to analyse the expression and production of these three chemokines within the joints of children with juvenile idiopathic arthritis (JIA) of the oligoarticular and polyarticular subtypes. All three of these chemokines are highly expressed at the level of mRNA, with the most significant increase in mRNA levels being demonstrated for CCL5 when compared with matched peripheral blood samples and controls. We show that high levels of all three chemokines are present in synovial fluid of children with JIA. We investigate the major source of CCL5 from inflammatory synovial cells, which we show to be CD8+ T cells. This CD8+ synovial T cell population has an unexpected phenotype that has not been described previously, being CCR7- yet predominantly CD28+ and CD45RA-. These cells contain high levels of stored intracellular CCL5, and rapid release of CCL5 takes place on T cell stimulation, without requiring new protein synthesis. In addition, we demonstrate that CCL5 is present in synovial biopsies from these patients, in particular on the endothelium of small and medium sized vessels. We believe this to be the first in depth analysis of these mediators of inflammation in JIA.