Reiss Y, Proudfoot A E, Power C A, Campbell J J, Butcher E C
Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
J Exp Med. 2001 Nov 19;194(10):1541-7. doi: 10.1084/jem.194.10.1541.
The chemokine thymus and activation-regulated chemokine (TARC; CCL17) is displayed by cutaneous (but not intestinal) venules, and is thought to trigger vascular arrest of circulating skin homing memory T cells, which uniformly express the TARC receptor CC chemokine receptor (CCR)4. Cutaneous T cell-attracting chemokine (CTACK; CCL27), expressed by skin keratinocytes, also attracts cutaneous memory T cells, and is hypothesized to assist in lymphocyte recruitment to skin as well. Here we show that chronic cutaneous inflammation induces CD4 T cells expressing E-selectin binding activity (a marker of skin homing memory cells) in draining lymph node, and that these E-selectin ligand+ T cells migrate efficiently to TARC and to CTACK. In 24 h in vivo homing assays, stimulated lymph node T cells from wild-type mice or, surprisingly, from CCR4-deficient donors migrate efficiently to inflamed skin; and an inhibitory anti-CTACK antibody has no effect on wild-type lymphocyte recruitment. However, inhibition with anti-CTACK monoclonal antibody abrogates skin recruitment of CCR4-deficient T cells. We conclude that CTACK and CCR4 can both support homing of T cells to skin, and that either one or the other is required for lymphocyte recruitment in cutaneous delayed type hypersensitivity.
趋化因子胸腺与活化调节趋化因子（TARC；CCL17）由皮肤（而非肠道）小静脉表达，被认为可触发循环中皮肤归巢记忆T细胞的血管停滞，这些T细胞均表达TARC受体CC趋化因子受体（CCR）4。皮肤角质形成细胞表达的皮肤T细胞吸引趋化因子（CTACK；CCL27）也可吸引皮肤记忆T细胞，据推测它也有助于淋巴细胞募集至皮肤。在此我们表明，慢性皮肤炎症可诱导引流淋巴结中表达E-选择素结合活性（皮肤归巢记忆细胞的一种标志物）的CD4 T细胞，并且这些E-选择素配体阳性T细胞可有效迁移至TARC和CTACK。在24小时的体内归巢试验中，来自野生型小鼠或令人惊讶地来自CCR4缺陷供体的受刺激淋巴结T细胞可有效迁移至炎症皮肤；并且一种抑制性抗CTACK抗体对野生型淋巴细胞募集没有影响。然而，用抗CTACK单克隆抗体抑制可消除CCR4缺陷T细胞向皮肤的募集。我们得出结论，CTACK和CCR4均可支持T细胞归巢至皮肤，并且在皮肤迟发型超敏反应中淋巴细胞募集需要其中之一。
