Study of T lymphocytes which develop in the extrathymic tissues.

人们已经接受T细胞识别与MHC相关的外来抗原。这种T细胞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，但其选择机制仍不清楚。在胸腺裸小鼠中，有报道称存在Thy-1<@D1+@>D1细胞。为了明确MHC限制性T细胞的生成是否真的需要胸腺特异性功能，我们进行了这项研究，以确定裸鼠胸腺内分化与正常胸腺内分化相比，the -1<@D1+@>D1淋巴细胞的分化阶段和特征。裸淋巴细胞表型表达研究表明，6周龄小鼠Thy-1<@D1+@>D1细胞为CD4<@D1-@>D1和CD8<@D1-@>D1。而在老年小鼠中，Thy-1<@D1+@>D1细胞比例增加，出现CD4<@D1+@>D1或CD8<@D1+@>D1细胞。这些CD4<@D1+@>D1和CD8<@D1+@>的d细胞也表达CD3，这表明它们表达T细胞抗绿受体（TCR）。事实上，利用TCR基因探针进行的southern blot分析显示，b链基因在表型成熟的裸T细胞中被重排。此外，这些裸T细胞表现出MLR和Con A反应能力。这些观察结果表明，功能成熟的T细胞可以从胸腺中发育出来。我们证明了T细胞分化途径的直接证据，从CD4<@D1-@>D1CD8<@D1-@>D1到CD4<@D1+@>D1或CD8<@D1+@>D1细胞到CD4<@D1+@>D1CD8<@D1+@>D1细胞。在裸鼠中，CD4<@D1+@>D1CD8<@D1+@>D1细胞未检出，但当CD4<@D1+@>D1CD8<@D1+@>D1胸腺细胞转移到裸鼠体内时，它们在CD4<@D1+@>D1和CD8<@D1+@>D1细胞中发育。这些观察结果表明，在胸腺外组织中，未成熟的T细胞可以发育为成熟的T细胞，而无需CD4<@D1+@>D1CD8<@D1+@>D1分化阶段。CD8<@D1+@>D1CD8<@D1+@>D1胸腺细胞是阴性选择的候选靶标。在这种情况下，裸鼠可能是研究耐受性机制的一个很好的模型。少

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