Differential expression of the chemokine receptors by the Th1- and Th2-type effector 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 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-gamma (IFN-gamma)-producing cells resided exclusively in CXCR3-expressing memory CD4+ T cells, although IFN-gamma 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.
Yamamoto
J
J
Department of Pediatrics, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
Adachi
Y
Y
Onoue
Y
Y
Adachi
Y S
YS
Okabe
Y
Y
Itazawa
T
T
Toyoda
M
M
Seki
T
T
Morohashi
M
M
Matsushima
K
K
Miyawaki
T
T
D000328:Adult; D003876:Dermatitis, Atopic / Q000097:blood / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D018793:Interleukin-13 / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D015848:Interleukin-5 / Q000096:biosynthesis / Q000235:genetics; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D054397:Receptors, CCR3; D054398:Receptors, CCR4; D019713:Receptors, CCR5 / Q000096:biosynthesis* / Q000235:genetics; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism*; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism*
C515350:CCR3 protein, human; C515354:CCR4 protein, human; C515187:CXCR3 protein, human; D018793:Interleukin-13; D015848:Interleukin-5; D054397:Receptors, CCR3; D054398:Receptors, CCR4; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D015847:Interleukin-4; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens; D013755:Tetradecanoylphorbol Acetate