Dermal Vγ4+ γδ T Cells Possess a Migratory Potency to the Draining Lymph Nodes and Modulate CD8+ T-Cell Activity through TNF-α Production
Dermal Vγ4+ γδ T Cells Possess a Migratory Potency to the Draining Lymph Nodes and Modulate CD8+ T-Cell Activity through TNF-α Production
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DOI：
10.1038/jid.2014.516
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发表时间：
2015-04-01
影响因子：
6.5
通讯作者：
Kabashima, Kenji
中科院分区：
文献类型：
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作者：
Nakamizo, Satoshi;Egawa, Gyohei;Kabashima, Kenji
大量的γ δ T细胞（γ δ T细胞）位于包括皮肤在内的上皮组织内。在小鼠中，表皮和真皮γ δ T细胞由不同的亚群组成，在皮肤免疫应答中具有特定作用。最近的一项研究表明，γ δ T细胞和皮肤树突状细胞从皮肤迁移到引流淋巴结（LN）。然而，目前尚不清楚它们是否调节淋巴结内的抗原特异性免疫应答。在此，我们研究了它们的性质和作用，在淋巴结使用牛分枝杆菌卡介苗（BCG）感染模型。体内细胞标记分析显示，大多数迁移亚群包括真皮V γ 4（+）细胞。该群体以Gi偶联趋化因子受体非依赖性方式从皮肤迁移到LN。通过去除V γ 4（+）细胞，CD 8（+）T细胞对BCG的结内扩增显著减弱。此外，体外分析显示，V γ 4（+）细胞产生TNF-α，并增强树突状细胞产生IL-12。综上所述，这些发现表明，真皮V γ 4（+）细胞是一个独特的亚群，具有迁移到皮肤引流淋巴结的能力，并增强其中的树突状细胞功能。
A large number of gamma delta T cells (gamma delta T cells) are located within epithelial tissues including the skin. In mice, epidermal and dermal gamma delta T cells consist of distinct subsets and have specific roles in cutaneous immune responses. A recent study demonstrated that gamma delta T cells and cutaneous dendritic cells migrate from the skin to the draining lymph nodes (LNs). However, it remains unclear whether they regulate the antigen-specific immune response within the LNs. Herein, we investigated their properties and role in the LNs using the Mycobacterium bovis bacille Calmette-Guerin (BCG) infection model. In vivo cell labeling analysis, revealed that most of the migratory subset comprised dermal V gamma 4(+) cells. This population transmigrated from the skin to the LNs in a Gi-coupled chemokine receptor independent manner. By depleting V gamma 4(+) cells, the intranodal expansion of CD8(+) T cell against BCG was significantly attenuated. In addition, in vitro analysis revealed that V gamma 4(+) cells produced TNF-alpha and enhanced IL-12 production by dendritic cells. Taken together, these findings suggest that dermal V gamma 4(+) cells are a unique subset that possesses a migratory potency to the skin-draining LNs and enhances the dendritic cell function therein.