Increased CCR4 expression on circulating CD4(+) T cells in ankylosing spondylitis, rheumatoid arthritis and systemic lupus erythematosus

Abstract

Previous studies have suggested that CCR4 is particularly important in the selective recruitment of various subsets of leucocytes in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In this study, we examined the percentage of CD4(+)/CCR4(+) T cells within circulating lymphocytes in active ankylosing spondylitis (AS), RA and SLE patients. The clinical significance of CCR4 expression as well as possible associations between the expression and serum levels of tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma and interleukin (IL)-10 were also examined. Our results showed that the percentage of CD4(+)/CCR4(+) T cells was significantly elevated in AS and RA patients as compared with normal controls. The percentage was also significantly higher in SLE patients who had received no treatment with glucocorticoids or cytotoxic drugs (untreated SLE) than that in controls. In addition, the percentage of CD4(+)/CCR4(+) T cells showed significant positive correlations with the Bath ankylosing spondylitis disease activity index (BASDAI) in AS and with the SLE disease activity index (SLEDAI) in untreated SLE. Of all the cytokines examined, the elevated serum IL-10 level was closely correlated with the percentage of CD4(+)/CCR4(+) T cells in AS, RA and untreated SLE. These results suggest that CCR4 may be crucial in the pathogenesis of AS, RA and SLE. The percentage of CD4(+)/CCR4(+) T cells can serve as a useful marker for the activity of AS and untreated SLE.

Fig. 1

CCR4 expression on circulating CD4⁺ T cells from the peripheral blood of normal controls and patients with AS, RA, untreated SLE (SLE0) and treated SLE (SLE1). A gate was drawn around lymphocytes defined by characteristic forward-angle and side-scatter profiles on flow cytometry, and the gated lymphocytes were analysed. The numbers in each upper right quadrant present the percentage of CD4⁺/CCR4⁺ T cells within circulating lymphocytes.

Fig. 2

(a) Percentage of CD4⁺/CCR4⁺ T cells within circulating lymphocytes (% CD4⁺/CCR4⁺ T cells) in controls, AS, RA, untreated SLE (SLE0) and treated SLE (SLE1). For each group, the single symbol on the right represents the median. The vertical thin bars indicate standard error (*P < 0·05; **P < 0·01). (b) The mean of the absolute number of lymphocytes, CD4⁺/CCR4⁺ T cells and non-CCR4⁺ lymphocytes in the blood in each group. For each group, the height of each bar represents the mean of the absolute number of lymphocytes, the black section represents that of CD4⁺/CCR4⁺ T cells and the white section represents that of non-CCR4⁺ lymphocytes.

Fig. 3

(a) Correlation between the Bath ankylosing spondylitis disease activity index (BASDAI) and the percentage of CD4⁺/CCR4⁺ T cells in the AS group (P < 0·05). (b) Correlation between the systemic lupus erythematosus disease activity index (SLEDAI) and the percentage of CD4⁺/CCR4⁺ T cells in untreated SLE (P < 0·01).