title: Dermal Vγ4(+) γδ T cells possess a migratory potency to the draining lymph nodes and modulate CD8(+) T-cell activity through TNF-α production.
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.
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nakamizo
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address: kaba@kuhp.kyoto-u.ac.jp.
authors.forename: Gyohei
authors.initials: G
authors.lastname: Egawa
authors.affiliation: Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Tomura
authors.affiliation: Department of Microbiology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Sakai
authors.affiliation: Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Soken
authors.initials: S
authors.lastname: Tsuchiya
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kitoh
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan; Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Honda
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Otsuka
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Saeko
authors.initials: S
authors.lastname: Nakajima
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Teruki
authors.initials: T
authors.lastname: Dainichi
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tanizaki
authors.affiliation: Department of Microbiology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Mitsuyama
authors.affiliation: Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Sugimoto
authors.affiliation: Department of Dermatology, Kido Hospital, Niigata, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kawai
authors.affiliation: Divisions of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Yoshikai
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Miyachi
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan; PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan. Electronic address: gyohei@kuhp.kyoto-u.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kabashima
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D002465:Cell Movement; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007801:Langerhans Cells / Q000166:cytology / Q000378:metabolism; D008027:Light; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009163:Mycobacterium bovis / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D012867:Skin / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma