Selective recruitment of CCR4-bearing Th2 cells toward antigen-presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine

Selective recruitment of CCR4-bearing Th2 cells toward antigen-presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine
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DOI:
10.1093/intimm/11.1.81
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发表时间:
1999-01-01
影响因子:
4.4
通讯作者:
Yoshie, O
Yoshie, O
中科院分区:
医学3区
文献类型:
--
作者:
Imai, T;Nagira, M;Yoshie, O

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辅助T细胞根据其细胞因子产生谱分为T(h)1和T(h)2亚群。T(h)1细胞参与细胞介导的免疫,而T(h)2细胞诱导体液应答。这两个亚群的选择性募集依赖于特异性粘附分子和特异性化学引诱物。在这里,我们证明了T细胞导向的CC趋化因子胸腺和活化调节趋化因子(TARC)是由粒细胞巨噬细胞集落刺激因子(GM-CSF)或IL-3处理的单核细胞大量产生的,特别是在IL-4存在的情况下,以及由GM-CSF + IL-4培养的单核细胞衍生的树突状细胞,TARC和另一种巨噬细胞/树突状细胞衍生的CC趋化因子巨噬细胞衍生的趋化因子(MDC)的受体是CCR 4,一种G蛋白偶联受体。发现CCR 4在成人外周血效应/记忆CD 4(+)T细胞中表达率接近20%。由TARC和MDC吸引的T细胞产生主要产生T(h)2型细胞因子、IL-4和IL-5的细胞系。分离的CCR 4(+)细胞而不是CCR 4(-)细胞也选择性地产生T(h)2型细胞系。当来自成人外周血的初始CD 4(+)T细胞在体外极化时,T(h)2型细胞选择性地表达CCR 4并向TARC和MDC强烈迁移。总之,CCR 4选择性地在T(h)2型T细胞上表达,并且抗原呈递细胞可以通过在T(h)2显性条件下产生TARC和MDC来募集表达CCR 4的Th 2细胞。
Helper T cells are classified into T(h)1 and T(h)2 subsets based on their profiles of cytokine production. T(h)1 cells are involved in cell-mediated immunity, whereas T(h)2 cells induce humoral responses. Selective recruitment of these two subsets depends on specific adhesion molecules and specific chemoattractants. Here, we demonstrate that the T cell-directed CC chemokine thymus and activation-regulated chemokine (TARC) was abundantly produced by monocytes treated with granulocyte macrophage colony stimulating factor (GM-CSF) or IL-3, especially in the presence of IL-4 and by dendritic cells derived from monocytes cultured with GM-CSF + IL-4, The receptor for TARC and another macrophage/dendritic cell-derived CC chemokine macrophage-derived chemokine (MDC) is CCR4, a G protein-coupled receptor. CCR4 was found to be expressed on similar to 20% of adult peripheral blood effector/memory CD4(+) T cells. T cells attracted by TARC and MDC generated cell lines predominantly producing T(h)2-type cytokines, IL-4 and IL-5. Fractionated CCR4(+) cells but not CCR4(-) cells also selectively gave rise to T(h)2-type cell lines. When naive CD4(+) T cells from adult peripheral blood were polarized in vitro, T(h)2-type cells selectively expressed CCR4 and vigorously migrated toward TARC and MDC. Taken together, CCR4 is selectively expressed on T(h)2-type T cells and antigen-presenting cells may recruit Th2 cells expressing CCR4 by producing TARC and MDC in T(h)2-dominant conditions.