Dermal Vγ4(+) γδ T cells possess a migratory potency to the draining lymph nodes and modulate CD8(+) T-cell activity through TNF-α production

真皮 Vγ4(+) γδ T 细胞具有向引流淋巴结迁移的能力,并通过 TNF-α 生成调节 CD8(+) T 细胞活性

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作者:Satoshi Nakamizo, Gyohei Egawa, Michio Tomura, Shunsuke Sakai, Soken Tsuchiya, Akihiko Kitoh, Tetsuya Honda, Atsushi Otsuka, Saeko Nakajima, Teruki Dainichi, Hideaki Tanizaki, Masao Mitsuyama, Yukihiko Sugimoto, Kazuhiro Kawai, Yasunobu Yoshikai, Yoshiki Miyachi, Kenji Kabashima

Abstract

A large number of gamma delta T cells (γδ T cells) are located within epithelial tissues including the skin. In mice, epidermal and dermal γδ T cells consist of distinct subsets and have specific roles in cutaneous immune responses. A recent study demonstrated that γδ 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-Guérin (BCG) infection model. In vivo cell labeling analysis revealed that most of the migratory subset comprised dermal Vγ4(+) cells. This population transmigrated from the skin to the LNs in a Gi-coupled chemokine receptor-independent manner. By depleting Vγ4(+) cells, the intranodal expansion of CD8(+) T cell against BCG was significantly attenuated. In addition, in vitro analysis revealed that Vγ4(+) cells produced TNF-α and enhanced IL-12 production by dendritic cells. Taken together, these findings suggest that dermal Vγ4(+) cells are a unique subset that possesses a migratory potency to the skin-draining LNs and enhances the dendritic cell function therein.

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