A keratinocyte-responsive γδ TCR is necessary for dendritic epidermal T cell activation by damaged keratinocytes and maintenance in the epidermis

A keratinocyte-responsive γδ TCR is necessary for dendritic epidermal T cell activation by damaged keratinocytes and maintenance in the epidermis
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DOI:
10.4049/jimmunol.172.6.3573
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发表时间:
2004-03-15
影响因子:
4.4
通讯作者:
Havran, WL
Havran, WL
中科院分区:
医学2区
文献类型:
--
作者:
Jameson, JM;Cauvi, G;Havran, WL

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一种独特的 T 淋巴细胞群,称为树突状表皮 T 细胞 (DETC),在胎儿发育过程中驻留在小鼠表皮中。 DETC 表达典型的 gammadelta TCR,Vgamma3/Vdelta1,它识别受损、应激或转化的角质形成细胞上表达的 Ag。最近,DETC被证明在复杂的伤口修复过程中发挥着关键作用。为了检查 DETC TCR 在 DETC 定位于表皮、皮肤维持和体内激活中的作用,我们分析了 TCRdelta(-/-) 小鼠的 DETC。与之前的报道不同,TCRdelta(-/-) 皮肤被发现缺乏任何 DETC,我们发现 TCRdelta(-/-) 小鼠具有表达 Alphata TCR 的 DETC,并具有多克隆 Vbeta 链库。 Alphabeta DETC 在动物的一生中不会保留,这表明 gammadelta TCR 对于皮肤中 DETC 的维持至关重要。尽管 Alphata DETC 可以响应直接刺激而被激活,但它们对角质形成细胞损伤没有反应。我们的结果表明,角质形成细胞响应性 TCR 对于响应角质形成细胞损伤而激活 DETC 以及维持表皮中的 DETC 是必需的。
A unique population of T lymphocytes, designated dendritic epidermal T cells (DETC), homes to the murine epidermis during fetal development. DETC express a canonical gammadelta TCR, Vgamma3/Vdelta1, which recognizes Ag expressed on damaged, stressed, or transformed keratinocytes. Recently, DETC were shown to play a key role in the complex process of wound repair. To examine the role of the DETC TCR in DETC localization to the epidermis, maintenance in the skin, and activation in vivo, we analyzed DETC in the TCRdelta(-/-) mouse. Unlike previous reports in which the TCRdelta(-/-) skin was found to be devoid of any DETC, we discovered that TCRdelta(-/-) mice have alphabeta TCR-expressing DETC with a polyclonal Vbeta chain repertoire. The alphabeta DETC are not retained over the life of the animal, suggesting that the gammadelta TCR is critical for the maintenance of DETC in the skin. Although the alphabeta DETC can be activated in response to direct stimulation, they do not respond to keratinocyte damage. Our results suggest that a keratinocyte-responsive TCR is necessary for DETC activation in response to keratinocyte damage and for DETC maintenance in the epidermis.