Ontogeny of T cells in skin : extrathymic development

皮肤中 T 细胞的个体发育：胸腺外发育

• 批准号: 07407024
• 负责人: TAMAKI Kunihiko
• 金额: $ 21.31万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07407024/
• 关键词: fetal skin; extrathymic T cell development; IL-7 transgenic; cytokine; Langerhans cells; T cells; mycosis fungoides; atopic dermatitis; マウス胎仔皮膚; RAG-1,2; 接着分子; ケラチノサイト; ランゲルハンス細胞; 皮膚; マウス

In this study, we identifiled novel dermal thy-1+ dendritic cells (Dermal Thy-1^+DC) and futher studied, 1) the ontogeny of T cells in the skin, 2) cytokine secretion by fetal keratinocytes (KC), 3) interaction between KC and Langerhans cells (LC). Dermal Thy-1^+DC are novel T cells found in murine dermis. Some of these cells expressed gammadeltaTCR and Vgamma3TCR.Howener, these cells seem to be composed of heterogeneous population. Murine fetal skin had abundant T cells and they showed dynamic change during fetal life in number as well as in morphology. Furthermore, murine fetal skin harbored immature macrophages. In the skin of IL-7 transgenic (tg) mice, dermatits developed with age. Immunohistohemical study of IL-7 tg mice revealed that epidermis and dermis harbored abundant alphabeta T cells and gammadelta T cells. Moreover, T cell repertoire analysis revealed these are heterogeneous. This may suggest that T cells in fetal skin differentiate in IL-7tg condition, and developed dermatitis in tg skin after birth. Further studies are needed to clarify this. Cytokine profiles of fetal skin was also stuied, and different profile between epidermis and dermis was found. The effect of KC derived cytokines on LC was also examined. From these studies, it is suggeted that fetal skin is a site of extrathymic T cell development, and that this may explain the T cell malignancy in the skin such as mycosis fungoides and the development of atopic dermatits.

在这项研究中，我们鉴定了新型真皮 thy-1+ 树突状细胞 (Dermal Thy-1^+DC) 并进一步研究了：1) 皮肤中 T 细胞的个体发育，2) 胎儿角质形成细胞 (KC) 的细胞因子分泌，3) KC 和朗格汉斯细胞 (LC) 之间的相互作用。真皮 Thy-1^+DC 是在小鼠真皮中发现的新型 T 细胞。其中一些细胞表达 gammadeltaTCR 和 Vgamma3TCR。然而，这些细胞似乎由异质群体组成。小鼠胎儿皮肤含有丰富的T细胞，它们在胎儿生命过程中在数量和形态上表现出动态变化。此外，小鼠胎儿皮肤含有未成熟的巨噬细胞。在 IL-7 转基因 (tg) 小鼠的皮肤中，皮炎随着年龄的增长而出现。 IL-7 tg 小鼠的免疫组织化学研究表明，表皮和真皮含有丰富的 Alphata T 细胞和 gammadelta T 细胞。此外，T 细胞库分析表明它们是异质的。这可能表明胎儿皮肤中的T细胞在IL-7tg条件下分化，并且在出生后tg皮肤中出现皮炎。需要进一步的研究来澄清这一点。还研究了胎儿皮肤的细胞因子谱，发现表皮和真皮之间存在不同的谱。还检查了 KC 衍生细胞因子对 LC 的影响。这些研究表明，胎儿皮肤是胸腺外 T 细胞发育的部位，这可以解释皮肤中的 T 细胞恶性肿瘤，如蕈样肉芽肿和特应性皮炎的发展。

项目成果

Tamaki K.et al: "Identification and characterization of novel dermal Thy-1 antigen-bearing dendritic cells in murine skin." J Invest Dermatol.106. 571-575 (1996)

Tamaki K.等人：“小鼠皮肤中新型真皮 Thy-1 抗原树突状细胞的鉴定和表征。”

Yasaka N, Furue M, Tamaki K: "Expression of cutuneons lynphooyte associated antgen defireed by monoclonal antibady HECA-452 on human Langerhaus cells" Jorunal of Dermatological Science. 11. 19-27 (1996)

Yasaka N、Furue M、Tamaki K：“单克隆抗体 HECA-452 在人类 Langerhaus 细胞上表达皮肤淋巴细胞相关抗原”，皮肤病学杂志。

K.Tamaki et al: "ldentification and characterization of novel derucel Thy-1^+-antigen bearing dendritic cells in murine skin" J Invest Deuwatol.106. 571-576 (1996)

K.Tamaki 等人：“小鼠皮肤中新型 derucel Thy-1^ -抗原携带树突状细胞的鉴定和表征”J Invest Deuwatol.106。

Furue M, Tamaki K et al: "Dysregulated expression of transforming growth factorβ and its typeI and type II receptors in basal-cell carcimone" International Journal of Cancer. 71. 505-509 (1997)

Furue M、Tamaki K 等人：“基底细胞癌中转化生长因子 β 及其 I 型和 II 型受体的表达失调”国际癌症杂志 71. 505-509 (1997)。

N.Yasaha,K.Tamaki et al: "Expression of cutaneous lymphocyte-associated antigen defined by monoclonel antibody HECA-452 on human langelas cells" J Deum.Sci.11. 19-27 (1996)

N.Yasaha,K.Tamaki 等人：“单克隆抗体 HECA-452 在人兰格拉斯细胞上表达皮肤淋巴细胞相关抗原”J Deum.Sci.11。