Departments of
* Pediatrics and
Dermatology, Faculty of Medicine, Toyama Medical and Pharmaceutical University; and
Department of Molecular Preventive Medicine, School of Medicine, University of Tokyo, Japan
Correspondence: Dr. Yuichi Adachi, Department of Pediatrics, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, Toyama 930-0194, Japan. E-mail: yadachi{at}ms.toyama-mpu.ac.jp
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 in 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 monoclonal
antibodies against CXCR3, CCR5, CCR3, and CCR4 disclosed that a
substantial proportion of memory (CD45RO+) CD4+
T cells in the blood of AD and normal patients expressed CXCR3, CCR5,
or CCR4, but expression of CCR3 on these cells was negligible.
Stimulation studies combined with intracellular cytokine staining
revealed that the cells capable of producing Th2 cytokines, 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-
(IFN-)-producing
cells resided exclusively in CXCR3-expressing memory CD4+ T
cells, although IFN- production was found in both memory
CD4+ T cells with and without CCR5 expression. We observed
that CCR4-expressing memory CD4+ T cells in the blood were
more increased in AD patients as compared with normal patients, whereas
CXCR3-expressing memory CD4+ T cells were present in a
lower frequency 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 identification of circulating Th1 and Th2
effector populations.
Key Words: CCR3 • CCR4 • CCR5 • CXCR3 • atopic dermatitis
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