CCR4+ memory CD4+ T lymphocytes are increased in peripheral blood and lesional skin from patients with atopic dermatitis

Background: Recent studies have reported that T(H)1 and T(H)2 cells express CXCR3 and CCR4, respectively. Objective: Our goal was to assess the association of CCR4 and CXCR3 expression with T(H)2 and T(H)1 cells and association of CCR4 and CXCR3 expression with inflammation in patients with atopic dermatitis (AD). Methods: Intracellular cytokine production and chemokine receptor expression in blood T cells were examined by flow cytometry. Immunohistochemical expression of chemokine receptors was also investigated in chronically lesional skin. Results: CCR4(+) and CXCR3(+) CD4(+) T cells predominantly produced IL-4 and IFN-gamma, respectively. Although the frequency of CXCR3(+) cells among CD4(+) CD45RO(+) T cells was similar for patients with AD (n = 29) and healthy control subjects (n = 19), patients with severe AD (n = 14) had a reduced frequency of CXCR3(+) cells. In contrast, the frequency of CCR4(+) cells and the CCR4/CXCR3 ratio were higher in patients with AD (n = 22) than healthy control subjects (n = 16) and correlated with disease severity of AD. The frequency of CCR4(+) cells correlated positively with eosinophil numbers and serum IgE levels, whereas the frequency of CXCR3(+) cells correlated inversely with eosinophil numbers. The frequency of CCR4(+) or CXCR3(+) cells was similar in patients with psoriasis (n = 6) and healthy control subjects. Immunohistochemical analysis showed that the frequency of CCR4(+) cells among CD4(+) T cells in chronically lesional skin of patients with AD (n = 9) was higher than that of patients with psoriasis (n = 4). Conclusion: Our data suggest the association of CCR4 expression with T(H)2 cells, the predominance of CCR4(+) cells in blood from patients with AD, and an important role of CCR4 in the migration of T(H)2 cells from blood into AD lesional skin.