Unique chemotactic response profile and specific expression of chemokine receptors CCR4 and CCR8 by CD4(+)CD25(+) regulatory T cells.
Unique chemotactic response profile and specific expression of chemokine receptors CCR4 and CCR8 by CD4(+)CD25(+) regulatory T cells.
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DOI：
10.1084/jem.194.6.847
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发表时间：
2001-09-17
期刊：
影响因子：
--
通讯作者：
D'Ambrosio D
中科院分区：
文献类型：
--
作者：
Iellem A;Mariani M;Lang R;Recalde H;Panina-Bordignon P;Sinigaglia F;D'Ambrosio D
趋化因子决定功能不同的T细胞亚群的区域运输。在啮齿动物和人类中，已经提出了一种独特的CD 4 + CD 25+细胞毒性T淋巴细胞抗原（CTLA）-4+调节性T细胞（Treg）亚群来控制外周耐受。然而，免疫抑制的分子基础和Treg细胞的运输特性仍然未知。在这里，我们确定了人血源性CD 4 + CD 25 + Treg细胞的趋化反应谱和趋化因子受体表达。发现这些Treg细胞对几种炎性和淋巴样趋化因子有强烈反应。Treg细胞特异性表达趋化因子受体CCR 4和CCR 8，并代表循环CD 4 + T细胞的主要亚群，其响应于趋化因子巨噬细胞衍生趋化因子（MDC）/CCL 22、胸腺和活化调节趋化因子（TARC）/CCL 17、I-309/CCL 1以及病毒因子vMIP-1（CCR 4和CCR 8的配体）。响应于CCL 1和CCL 22而迁移的血源性CD 4 + T细胞表现出降低的同种异体增殖反应，这取决于迁移群体中Treg细胞频率的增加。重要的是，成熟树突状细胞通过分泌CCR 4配体CCL 17和CCL 22优先吸引循环CD 4 + T细胞中的Treg细胞。总之，这些结果表明，CCR 4和/或CCR 8可以引导Treg细胞到次级淋巴组织和发炎区域中的抗原呈递位点，以减弱T细胞活化。
Chemokines dictate regional trafficking of functionally distinct T cell subsets. In rodents and humans, a unique subset of CD4+CD25+ cytotoxic T lymphocyte antigen (CTLA)-4+ regulatory T cells (Treg) has been proposed to control peripheral tolerance. However, the molecular basis of immune suppression and the trafficking properties of Treg cells are still unknown. Here, we determined the chemotactic response profile and chemokine receptor expression of human blood-borne CD4+CD25+ Treg cells. These Treg cells were found to vigorously respond to several inflammatory and lymphoid chemokines. Treg cells specifically express the chemokine receptors CCR4 and CCR8 and represent a major subset of circulating CD4+ T cells responding to the chemokines macrophage-derived chemokine (MDC)/CCL22, thymus and activation-regulated chemokine (TARC)/CCL17, I-309/CCL1, and to the virokine vMIP-I (ligands of CCR4 and CCR8). Blood-borne CD4+ T cells that migrate in response to CCL1 and CCL22 exhibit a reduced alloproliferative response, dependent on the increased frequency of Treg cells in the migrated population. Importantly, mature dendritic cells preferentially attract Treg cells among circulating CD4+ T cells, by secretion of CCR4 ligands CCL17 and CCL22. Overall, these results suggest that CCR4 and/or CCR8 may guide Treg cells to sites of antigen presentation in secondary lymphoid tissues and inflamed areas to attenuate T cell activation.
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影响因子：
15.3
作者：
Endres, MJ;Garlisi, CG;Hedrick, JA
通讯作者：
Hedrick, JA
影响因子：
64.8
作者：
Sallusto, F;Lenig, D;Lanzavecchia, A
通讯作者：
Lanzavecchia, A
DOI：
10.1016/s0167-5699(99)01510-8
发表时间：
1999-10-01
期刊：
IMMUNOLOGY TODAY
影响因子：
--
作者：
Groux, H;Powrie, F
通讯作者：
Powrie, F
DOI：
10.1016/s0167-5699(00)01590-5
发表时间：
2000-04-01
期刊：
IMMUNOLOGY TODAY
影响因子：
--
作者：
D'Ambrosio, D;Iellem, A;Sinigaglia, F
通讯作者：
Sinigaglia, F
影响因子：
32.4
作者：
Smith, A;Wikstrom, ME;Fazekas de St Groth, B
通讯作者：
Fazekas de St Groth, B