Extrathymic T cell differentiation and role of hepatic sinusoids

胸腺外 T 细胞分化和肝窦的作用

• 批准号: 02807056
• 负责人: ABO Toru
• 金额: $ 0.96万
• 依托单位: Niigata University School of Medicine (1991)Tohoku University (1990)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02807056/
• 关键词: extrathymic T cells; hepatic sinusoids; intermediate TCR; alpha beta T cells; tumor immunity; NK cells; Tリンパ球; 胸腺外分化; 肝類洞; αβT細胞; γδT細胞; intermediate TcR; ヌ-ドマウス; 胸腺摘出

There exists a considerable number of unique T lymphocytes in the periphery in congenitally athymic nude mice, and in aged humans and animals with the in-voluted thymus. It is, therefore, suggested by several investigators that the extrathymic pathway of T cell differentiation may be present somewhere. We have recently demonstrated that such extrathymic T cell differentiation occurs in the hepatic sinusoids in humans and mice. This pathway of T cell differentiation resides phylogenetically earlier than the intrathymic pathway of T cell differentiation. Before and after thymic development, extrathymic T cells might work as the surveillance system for atypical cells generated in vivo by virtue of their autoreactivity. Extrathymic T cells have alpha beta TCR (and gamma delta TCR) of intermediate intensity and contain many auto-reactive T cell clones. The existence of the hepatic pathway could clearly explain the phenomenon "breakdown of self-tolerance", and occupies an important position of the immunology for aging, autoimmune disease, malignancy, bacterial infection, transplantation and allergy (immediate hypersensitivity).

在先天性无胸腺裸鼠和老年胸腺发育不良的人和动物外周血中，存在大量独特的T淋巴细胞。因此，一些研究人员提出，胸腺外T细胞分化的途径可能存在于某个地方。我们最近已经证明，这种胸腺外T细胞分化发生在人类和小鼠的肝窦中。这种T细胞分化的途径在系统发育上早于胸腺内的T细胞分化途径。胸腺发育前后，胸腺外T细胞可能通过自身反应性对体内产生的非典型细胞起到监视作用。胸腺外T细胞具有中等强度的α-β-TCR(和γ-β-TCR)，并含有许多自身反应性T细胞克隆。肝通路的存在可以清楚地解释“自我耐受崩溃”的现象，在衰老、自身免疫性疾病、恶性肿瘤、细菌感染、移植和变态反应(即刻超敏)等免疫学中占有重要地位。

项目成果

T. Abo, et al.: "Induction of human TcR gamma delta + nd TcR gamma delta -CD2+CD3- double negative lymphocytes by bacterial stimulation." Int. Immunol.2. 775-785 (1990)

T. Abo 等人：“通过细菌刺激诱导人 TcR gamma delta 和 TcR gamma delta -CD2 CD3- 双阴性淋巴细胞。”

安保 徹: "Induction of human TCRγδ^+ and TcR γδ^ーCD2^+CD3^ー double negative lymphocytes by bacterial stimulation" Int.Immunol.2. 775-785 (1990)

Toru Anbo：“通过细菌刺激诱导人 TCRγδ^+ 和 TcR γδ^－CD2^+CD3^－ 双阴性淋巴细胞” Int.Immunol.2 (1990)。

S.Saki,et al.: "Unusual α βーT cells expanded in autoimmune lpr mice are probably a counterpart of normal T cells in the liver." J.Immunol.147. 1214-1221 (1991)

S.Saki 等人：“自身免疫 lpr 小鼠中扩增的异常 α β-T 细胞可能是肝脏中正常 T 细胞的对应物。”J.Immunol.1214-1221 (1991)。

安保 徹: "Liver is a possible site for the proliferation of abnomal CD3^+4^ー8^ー doubleーnegative lymphocytes in autoimmue MRLー1pr/1pr" J.Exp.Med.172. 7-12 (1990)

Toru Anbo：“肝脏是自身免疫 MRL－1pr/1pr 中异常 CD3^+4^－8^－ 双阴性淋巴细胞增殖的可能部位”J.Exp.Med.172 (1990)。

安保 徹: "Generation of forbidden T cell oligoclones in the liver of mice infected with bacteria" J.Exp.Med.(1991)

Toru Anbo：“在感染细菌的小鼠肝脏中生成禁止的 T 细胞寡克隆”J.Exp.Med.(1991)