Analysis of Mechanisms by Which T Cells Migrate to the Epidermis

T细胞迁移至表皮的机制分析

• 批准号: 01480268
• 负责人: SHIOHARA Tetsuo
• 金额: $ 4.03万
• 依托单位: Kyorin University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-01480268/
• 关键词: Epidermotropism; T-cell clones; LFA-1; Thy 1^+ epidermal cells; Thymus dependency; Thy1^+epidermal cell; 胸腺依存性; Thy1^+ EC; サイトカインレセプタ-; 表皮由来サイトカイン; ILー6; GMーCSF; Cell adhesion nolecule

We previously established murine T cell clones with special tropism the epidermis both in vitro in vivo. Using these T cell clones, we attempted to elucidate the mechanisms by which certain T cells preferentially migrate to the epidemis.1. To determine which cell adhesion molecules are involved in epidermotrpoism of T cells, the expression of rariaus T-cell surface molecules on epidermotropic and non-epidermotropic T cell clones was examined by flow cytometric analysis. The results showed that LFA-1 was preferentially expressed on the surface of epidermotropic T cell clones, while non-epidermotropic T cell clones were negative or weakly positive for LFA-1.2. These epidermotropic T cells showed directional migration toward the epidermis in an in vitro migration assay under agar gel. Antibody inhibition studies demonstrated that of various mAb to T-cell surface molecules only anti-LEA-1 mAb completely inhibited the in vitro migartion of the T cells toward the epidermis. These findings indicate that the LFA-1 also plays an important role in directing T cell migration to the epidermis.3. It was found that epidermal structures that had spontaneously recovered from the destruction induced by inteademal injection of the epidermotropic T cells became resistant to subsequent attempts to induce the destruction by the T cells. This resistance correlated well with the great increase in Thy 1^+ epidermal cell numbers. The resistance was never induced in athymic nude mice and adult thymectomized mice. The expansion of the Thy 1^+ EC that mature in thymus would be crucial to the induction of the resistance.

我们之前在体外和体内建立了对表皮具有特殊趋向性的小鼠T细胞克隆。利用这些 T 细胞克隆，我们试图阐明某些 T 细胞优先迁移到表皮的机制。1。为了确定哪些细胞粘附分子参与 T 细胞的表皮分化，通过流式细胞分析检查了亲表皮性和非亲表皮性 T 细胞克隆上稀有 T 细胞表面分子的表达。结果显示，LFA-1优先表达于亲表皮性T细胞克隆表面，而非亲表皮性T细胞克隆LFA-1.2呈阴性或弱阳性。在琼脂凝胶下的体外迁移试验中，这些亲表皮 T 细胞显示出向表皮的定向迁移。抗体抑制研究表明，在针对 T 细胞表面分子的各种 mAb 中，只有抗 LEA-1 mAb 完全抑制 T 细胞向表皮的体外迁移。这些发现表明LFA-1在引导T细胞迁移至表皮方面也发挥着重要作用。3．结果发现，从真皮内注射亲表皮T细胞诱导的破坏中自发恢复的表皮结构对随后诱导T细胞破坏的尝试产生了抵抗力。这种抵抗力与 Thy 1^+ 表皮细胞数量的大幅增加密切相关。无胸腺裸鼠和成年胸腺切除小鼠从未诱导出抵抗力。胸腺中成熟的 Thy 1^+ EC 的扩展对于诱导耐药性至关重要。

项目成果

Tetsuo Shiohara, Noriko Moriya, Chie Gotoh, Jun Hayakawa, Hiromichi Ishikawa, Kaj Saizawa, and Masaji Nagashima.: "Loss of epidermal integrity by T cell-mediated attack induces long-term local resistance to subsequent attack. II. Thymus dependency in the

Tetsuo Shiohara、Noriko Moriya、Chie Gotoh、Jun Hayakawa、Hiromichi Ishikawa、Kaj Saizawa 和 Masaji Nagashima。：“T 细胞介导的攻击导致表皮完整性丧失，导致对后续攻击的长期局部抵抗力。II. 胸腺依赖性

Shiohara,T.et al.: "Evidence for involvement of lymphocyte functionーassociated antigen1 in T cell migration to epidermis." J.Immunol.146. 840-845 (1991)

Shiohara, T. 等人：“淋巴细胞功能相关抗原 1 参与 T 细胞迁移至表皮的证据。”J.Immunol.146 (1991)。

Shiohara,T.et al.: "Loss of epidernal integrity by T cellーmediated attack induces longーtern local resistance to subsequent attack.I.Induction of resistance correlates with increases in Thy1^+epidermal cell numbers." J.Exp.Med.171. 1027-1041 (1990)

Shiohara, T. 等人：“T 细胞介导的攻击导致表皮完整性丧失，从而诱导对后续攻击的长期局部抵抗。I. 抵抗力的诱导与 Thy1^+ 表皮细胞数量的增加相关。”医学171。1027-1041（1990）

Shiohara,T.et al.: "In vitro migration of L3T4^+ cloned T cells to epidermis:Possible role for keratinocyte-derived factors" J.Invest.Dermatol.92. 360-365 (1989)

Shiohara,T.et al.：“L3T4^ 克隆 T 细胞体外迁移至表皮：角化细胞衍生因子的可能作用”J.Invest.Dermatol.92。

Tetsuo Shiohara.: "Skin as the unique immunologic organ." Clin. Immunol.vol. 23. 73-84 (1991)

Tetsuo Shiohara：“皮肤是独特的免疫器官。”