Abstract
The aim of the study was to characterise CCR7+ and CCR7- memory T cells infiltrating the inflamed joints of patients with juvenile idiopathic arthritis (JIA) and to investigate the functional and anatomical heterogeneity of these cell subsets in relation to the expression of the inflammatory chemokine receptors CXCR3 and CCR5. Memory T cells freshly isolated from the peripheral blood and synovial fluid (SF) of 25 patients with JIA were tested for the expression of CCR7, CCR5, CXCR3 and interferon-γ by flow cytometry. The chemotactic activity of CD4 SF memory T cells from eight patients with JIA to inflammatory (CXCL11 and CCL3) and homeostatic (CCL19, CCL21) chemokines was also evaluated. Paired serum and SF samples from 28 patients with JIA were tested for CCL21 concentrations. CCR7, CXCR3, CCR5 and CCL21 expression in synovial tissue from six patients with JIA was investigated by immunohistochemistry. Enrichment of CD4+, CCR7- memory T cells was demonstrated in SF in comparison with paired blood from patients with JIA. SF CD4+CCR7- memory T cells were enriched for CCR5+ and interferon-γ+ cells, whereas CD4+CCR7+ memory T cells showed higher coexpression of CXCR3. Expression of CCL21 was detected in both SF and synovial membranes. SF CD4+ memory T cells displayed significant migration to both inflammatory and homeostatic chemokines. CCR7+ T cells were detected in the synovial tissue in either diffuse perivascular lymphocytic infiltrates or organised lymphoid aggregates. In synovial tissue, a large fraction of CCR7+ cells co-localised with CXCR3, especially inside lymphoid aggregates, whereas CCR5+ cells were enriched in the sublining of the superficial subintima. In conclusion, CCR7 may have a role in the synovial recruitment of memory T cells in JIA, irrespective of the pattern of lymphoid organisation. Moreover, discrete patterns of chemokine receptor expression are detected in the synovial tissue.
Highlights
Migration and accumulation of memory T cells in the synovium is a critical step in the pathogenesis of chronic arthritides [1,2,3]
Phenotypic and functional characterisation of CCR7+ and CCR7- CD4+ memory T cells isolated from synovial fluid (SF) Expression of CCR7 on CD4+ memory T cells from the peripheral blood (PB) and SF of 10 patients with juvenile idiopathic arthritis (JIA) was investigated by threecolour immunofluorescence analysis and compared with that detected on the same PB cell subset from eight agematched healthy controls
Even a variable proportion of SF memory CD4+ T cells are positive for CCR7; this subpopulation is clearly enriched in CCR7- cells in comparison with paired PB
Summary
Migration and accumulation of memory T cells in the synovium is a critical step in the pathogenesis of chronic arthritides [1,2,3]. From a functional point of view, chemokines can be broadly classified into two groups: inflammatory and homeostatic [4]. The inflammatory chemokines are induced by proinflammatory stimuli and control the migration of leukocytes to the site of inflammation. CCR5 and CXCR3 are classical examples of receptors for inflammatory chemokines [5]. The homeostatic chemokines regulate the basal traffic of lymphocytes and other leukocytes through peripheral lymphoid tissues. CCR7 is an example of a receptor for homeostatic chemokines. The CCR7 chemokine receptor has been identified as an important marker of memory T cell differentiation. It has been proposed that CCR7+ memory T cells represent a pool of 'central' memory T cells homing to lymph nodes, where they undergo further differentiation into CCR7- memory T cells, which migrate to the peripheral tissues to perform their effector functions [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
