Differential expression of the chemokine receptors by the Th1-and Th2-typeeffector populations within circulating CD4(+) T cells

The in vitro studies have proposed that human Th1 cells favor expression of CXCR3 or CCR5, whereas Th2 cells favor CCR3 and CCR4. In this study, the i n vivo relevance of expression of these chemokine receptors on Th cells was investigated in patients with atopic dermatitis (AD) as the Th2-dominated disorder and nonatopic normal individuals. Flow-cytometric analysis using m onoclonal antibodies against CXCR3, CCR5, CCR3, and CCR4 disclosed that a s ubstantial proportion of memory (CD45RO(+)) CD4(+) T cells in the Mood of A D and normal patients expressed CXCR3, CCR5, or CCR4, but expression of CCR 3 on these cells was negligible, Stimulation studies combined with intracel lular cytokine staining revealed that the cells capable of producing Th2 cy tokines, such as interleukin-4 (IL-4), IL-5, and IL-13, were restricted to the CCR4-expressing population within memory CD4(+) T cells. Concerning Th1 cytokine production, interferon-gamma (IFN-gamma)-producing cells resided exclusively in CXCR3-expressing memory CD4(+) T cells, although IFN-gamma p roduction was found in both memory CD4(+) T cells with and without CCR5 exp ression. We observed that CCR4-expressing memory CD4(+) T cells in the bloo d were more increased in AD patients as compared with normal patients, wher eas CXCR3-expressing memory CD4(+) T cells were present in a lower frequenc y in AD than seen in normal patients. These results suggest that CXCR3 and CCR4, but not CCR5 or CCR3, appear to serve as the useful markers for ident ification of circulating Th1 and Th2 effector populations.