A role for the integrin α6β1 in the differential distribution of CD4 and CD8 T-cell subsets within the rheumatoid synovium

Abstract

Objective. CD4 and CD8 T-cell subsets accumulate in distinct microdomains within the inflamed rheumatoid synovium. The molecular basis for their differential distribution remains unclear. Since chemokines and adhesion molecules play an important role in the positioning of leucocytes at sites of inflammation, we tested the hypothesis that the differential expression and function of chemokine and/or adhesion molecules explains why CD4+ T cells accumulate within perivascular cuffs, whereas CD8+ T cells distribute diffusely within the tissue. Methods. Expression of an extensive panel of chemokine receptors and adhesion molecules on matched CD4+ and CD8+ T cells from peripheral blood (PB) and synovial fluid (SF) was analysed by multicolour flow cytometry. Migration assays and flow-based adhesion assays were used to assess the functional consequences of any differences in the expression of chemokine and adhesion receptors. Results. CD4+ and CD4+ T cells from PB and SF expressed unique yet consistent patterns of chemokine and adhesion receptors. SF CD8+ T cells were much less promiscuous in their expression of chemokine receptors than SF CD4+ T cells. The α6β1 integrin was highly expressed on PB CD4+ T cells, but not on PB CD8+ T cells. Laminin, the ligand for α6β1, retained CD4+ T cells, but less so CD8+ T cells, within inflamed synovial tissue. Conclusion. Infiltrating PB CD4+ Tcells, but not CD8+ T cells, express functional levels of the α6β1 integrin. We propose that this leads to their retention within the rheumatoid synovium in perivascular cuffs, which are defined and delineated by the expression of laminin. © The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.