Costimulation of dendritic epidermal gammadelta T cells by a new NKG2D ligand expressed specifically in the skin.

Costimulation of dendritic epidermal gammadelta T cells by a new NKG2D ligand expressed specifically in the skin.
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DOI:
10.4049/jimmunol.0802439
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发表时间:
2009-04-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Raulet DH
Raulet DH
中科院分区:
其他
文献类型:
--
作者:
Whang MI;Guerra N;Raulet DH

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树突状表皮T细胞(Dendritic epidermal T cells, DETCs)是一种高度特化的γδ T细胞,存在于小鼠皮肤中,参与伤口愈合和肿瘤监测。尽管在这些细胞上表达了其他刺激受体,但涉及激活的机制主要集中在DETC表达的不变的Vγ3-Vδ1 TCR上。所有DETC也表达活化的NKG2D受体,但NKG2D在DETC活化中的作用尚不清楚,在皮肤中功能性表达的NKG2D配体的身份也不清楚。在这里,我们记录了NKG2D配体的克隆,该配体在皮肤和培养的角质形成细胞中特异性表达,并证明了其在DETC和自然杀伤细胞激活中的作用。在NKG2D配体中,该配体在培养的角质形成细胞中表达上调是独一无二的,它与NKG2D的相互作用对于DETC的激活是必不可少的。重要的是,研究表明,NKG2D的参与并不足以激活DETC,而是提供了一个共刺激信号,然而,该信号对于角化细胞刺激激活DETC至关重要。
Dendritic epidermal T cells (DETCs) are a highly specialized population of γδ T cells that resides in the murine skin and participates in wound healing and tumor surveillance. Despite the expression of other stimulatory receptors on these cells, mechanisms involving activation have focused primarily on the invariant Vγ3-Vδ1 TCR expressed by DETC. All DETC also express the activating NKG2D receptor, but the role of NKG2D in DETC activation remains unclear, as does the identity of NKG2D ligands that are functionally expressed in the skin. Here we document the cloning of an NKG2D ligand that is expressed specifically in the skin and in cultured keratinocytes, and demonstrate its role in the activation of DETC and natural killer cells. The ligand is unique among NKG2D ligands in being upregulated in cultured keratinocytes, and its interaction with NKG2D is essential for DETC activation. Importantly, it is shown that engagement of NKG2D is not sufficient to activate DETC, but instead provides a costimulatory signal that is nevertheless essential for activating DETC in response to stimulation with keratinocytes.
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