Study of T lymphocytes which develop in the extrathymic tissues.

研究胸腺外组织中发育的 T 淋巴细胞。

• 批准号: 61480139
• 负责人: HABU Sonoko
• 金额: $ 3.58万
• 依托单位: Tokai 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: 1986
• 资助国家: 日本
• 起止时间: 1986 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-61480139/
• 关键词: Nude mouse; Thymus-independent T cells; Immature T cells; Cell surface molecules; T細胞抗原レセプター; T細胞分化過程; 胸腺; CD_4; CD_8; CD_3; T細胞レセプター; Thy-1陽性細胞; T細胞表面マーカー; 胸腺外T細胞分化

It has been accepted that T cells recognize forein antigens in association with MHC. This T cell nature is postulated to be selectively generated during the intrathymic differentiation. despite many trials, the selection mechanism is still remained unclear. In athymic nude mice, the presence of Thy-1<@D1+@>D1 cells has been reported. To clarify whether the thymus specific function is really required for the MHC restricted T cell generation, we adressed this study to identify the differentiation stages and the characteristics of The-1<@D1+@>D1 lymphocytes in the nude mice in comparison with normal intrathymic differentiation. The study of phenotype expression in the nude lymphocytes demonstrated that the Thy-1<@D1+@>D1cells are CD4<@D1-@>D1 and CD8<@D1-@>D1 in 6-week old mice. However, in aged mice, the proportion of Thy-1<@D1+@>D1cells increased and CD4<@D1+@>D1 or CD8<@D1+@>D1cells appeared. These CD4<@D1+@>D1 and CD8<@D1+@>Dcells also expressed CD3, implying they express T cell antig … More en receptor(TCR). In fact, sourthern blot analysis using TCR gene probe showed that B-chain genes are rearranged in the phenotypically mature nude T cells. In addition, these nude T cells showed MLR and Con A reactive ability. These observations indicate that functionally mature T cells can delevop out of the thymus. We demonstrated a direct evidence of T cell differentiation pathway from CD4<@D1-@>D1CD8<@D1-@>D1 go CD4<@D1+@>D1 or CD8<@D1+@>D1 cells through CD4<@D1+@>D1CD8<@D1+@>D1 cells in the thymus. In nude mice, CD4<@D1+@>D1CD8<@D1+@>D1 cells were not detectable but when CD4<@D1+@>D1CD8<@D1+@>D1 thymocytes were transfered into the nude mice, they develop in CD4<@D1+@>D1 and CD8<@D1+@>D1 cells. These observations suggest that in the extrathymic tissued, immature T cells may develop into mature T cells without CD4<@D1+@>D1CD8<@D1+@>D1 differentiation stage. CD8<@D1+@>D1CD8<@D1+@>D1 thymocytes are candidates of targets for negative selection. If that is a case, the nude mouse may be a good model to study tolerance mechanism. Less

T细胞识别与MHC相关的forein抗原已被公认。这种T细胞的性质被认为是在胸腺内分化过程中选择性产生的。尽管进行了多次试验，但甄选机制仍不明确。在无胸腺裸小鼠中，Thy-1<@D1+@>D1细胞的存在已被报道。为了阐明胸腺特异性功能是否是MHC限制性T细胞产生的必要条件，我们研究了裸鼠胸腺内T淋巴细胞的分化阶段和分化特性，并与正常胸腺内分化进行了比较。裸淋巴细胞表型表达的研究表明，6周龄小鼠Thy-1<@D1+@> D1细胞为CD 4 <@D1-@>D1和CD 8 <@D1-@>D1。而老年小鼠Thy-1<@D1+@> D1细胞比例增加，出现CD 4 <@D1+@>D1或CD 8 <@D1+@> D1细胞。这些CD 4 <@D1+@>D1和CD 8 <@D1+@> D细胞也表达CD 3，这意味着它们表达T细胞抗原， ...更多信息 en受体（TCR）。事实上，使用TCR基因探针的sourceBlot分析表明，在表型成熟的裸T细胞中，B链基因重排。此外，这些裸T细胞具有MLR和ConA反应能力。这些观察结果表明，功能成熟的T细胞可以从胸腺中排出。我们证明了胸腺中T细胞从CD 4 <@D1-@> D1、CD 8 <@D1-@>D1到CD 4 <@D1+@>D1或CD 8 <@D1+@>D1再到CD 4 <@D1+@> D1、CD 8 <@D1+@> D1的分化途径。在裸鼠体内未检测到CD 4 <@D1+@> D1 CD 8 <@D1+@>D1细胞，而将CD 4 <@D1+@> D1 CD 8 <@D1+@>D1胸腺细胞转入裸鼠体内后，则出现CD 4 <@D1+@>D1和CD 8 <@D1+@>D1细胞。这些观察结果表明，在胸腺外组织中，未成熟的T细胞可以在没有CD 4 <@D1+@> D1 CD 8 <@D1+@>D1分化阶段的情况下发育为成熟的T细胞。CD 8 <@D1+@> D1 CD 8 <@D1+@>D1胸腺细胞是阴性选择的候选靶细胞。如果是这样的话，裸鼠可能是研究耐受机制的良好模型。少

项目成果

S.Habu: Immunological Reviews. 92. 67-80 (1986)

S.Habu：免疫学评论。

G.Suzuki: J.Immunol.

G.铃木：J.Immunol。

Y. Takeuchi: "Cytosporin A and anti-Ia antibody cause maturation defect of CD4^+8^-cells in the organ cultured fetal thymuses." Immunology. (1989)

Y. Takeuchi：“细胞孢菌素 A 和抗 Ia 抗体会导致器官培养的胎儿胸腺中 CD4^8^-细胞的成熟缺陷。”

S.Habu: Acta Histochem.cytochem. 20. 251-260 (1987)

S.Habu：组织化学学报.细胞化学。

H. Tamauchi: "CD4^+CD8^+thymocytes develop into CD4 or CD8 single positive cells in the athymic nude mice." Eur.J. Immunol.18. 1859-1862 (1988)

H. Tamauchi：“在无胸腺裸鼠中，CD4^ CD8^ 胸腺细胞发育为 CD4 或 CD8 单阳性细胞。”