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[T细胞白血病抗原,FT - 1和FT - 2]

[T cell leukemia antigens, FT-1 and FT-2].

作者信息

Kasai M, Tokunaga T

出版信息

Gan To Kagaku Ryoho. 1986 Mar;13(3 Pt 2):806-11.

PMID:3083784
Abstract

The understanding of the differentiation process of lymphocytes in the embryonic thymus has been based on extrapolation from adult thymic lymphocytes. The study presented here was mainly concerned with the new cell surface antigens designated FT (FT-1, FT-2), which are expressed on fetal thymocytes of all mouse strains examined, but not on thymocytes or any other lymphoid cells of adult mice. One of the interesting features of FT antigens is the timing of their expression in connection with the ontogeny of thymic lymphocytes. A majority of fetal thymocytes at the 13th day of gestation express FT antigens, whereas no positive cells are found in fetal liver. Therefore, FT antigens seem to appear as soon as the stem cells have reached the thymus. The proportion of FT+ cells then declines sharply with increase in the time of gestation, while Thy-1+ cells increase in inverse proportion. All of these results seem to support the idea that the thymocytes expressing FT antigens are replaced with Thy-1+ thymocytes, although the possibility of the transition from FT+ to Thy-1+ cells cannot be excluded. It was also demonstrated that fetal thymocytes are heterogeneous with respect to the expression of FT-1 and FT-2 antigens. Especially, thymic lymphocytes at the earlier stages of ontogeny can be divided into at least three subpopulations, FT-1+2+, FT-1+2- and FT-1-2-. With the emergence of Lyt antigens, these subpopulations seem to differentiate and acquire far more complicated features. Such cellular heterogeneity probably reflects the complexed events like selection, deletion or amplification occurring in the embryonic thymus. Another interesting aspect of FT antigens is their reappearance on the surface of thymic leukemia cells. Biochemical studies have indicated that the molecular weight of FT-1 antigen on leukemia cells is about 100,000 by means of biosynthetic labeling with either [3H]-galactose or [35S]-methionine. FT-1 antigen on fetal thymocytes also appeared as a major band with m.w. 100,000. Two-dimensional gel electrophoresis revealed that FT-1 antigenic determinants appear to reside on a family of glycoproteins with extensive charge heterogeneity. All of these results suggest that FT antigens, especially FT-1 antigen, will be useful markers for understanding the mechanism underlying the activation of normally silent genetic information in leukemia cells. In summary, further biochemical and genetic analysis of FT antigens will contribute to an understanding of the ontogenic development of T cells as well as the leukemogenesis of T cell leukemias.

摘要

对胚胎胸腺中淋巴细胞分化过程的理解一直基于从成年胸腺淋巴细胞进行的推断。本文所呈现的研究主要关注一种名为FT(FT - 1、FT - 2)的新细胞表面抗原,在所检测的所有小鼠品系的胎儿胸腺细胞上均有表达,但在成年小鼠的胸腺细胞或任何其他淋巴细胞上均未表达。FT抗原的一个有趣特征是其表达时间与胸腺淋巴细胞的个体发生相关。妊娠第13天的大多数胎儿胸腺细胞表达FT抗原,而在胎儿肝脏中未发现阳性细胞。因此,FT抗原似乎在干细胞到达胸腺后就立即出现。随着妊娠时间的增加,FT⁺细胞的比例急剧下降,而Thy - 1⁺细胞则呈反比增加。所有这些结果似乎都支持这样一种观点,即表达FT抗原的胸腺细胞被Thy - 1⁺胸腺细胞所取代,尽管不能排除从FT⁺细胞转变为Thy - 1⁺细胞的可能性。研究还表明,胎儿胸腺细胞在FT - 1和FT - 2抗原的表达方面具有异质性。特别是,个体发生早期阶段的胸腺淋巴细胞至少可分为三个亚群,即FT - 1⁺2⁺、FT - 1⁺2⁻和FT - 1⁻2⁻。随着Lyt抗原的出现,这些亚群似乎发生分化并获得更为复杂的特征。这种细胞异质性可能反映了胚胎胸腺中发生的诸如选择、缺失或扩增等复杂事件。FT抗原的另一个有趣方面是它们在胸腺白血病细胞表面的重新出现。生化研究表明,通过用[³H] - 半乳糖或[³⁵S] - 甲硫氨酸进行生物合成标记,白血病细胞上FT - 1抗原的分子量约为100,000。胎儿胸腺细胞上的FT - 1抗原也表现为一条主要条带,分子量为100,000。二维凝胶电泳显示,FT - 1抗原决定簇似乎存在于一组具有广泛电荷异质性的糖蛋白上。所有这些结果表明,FT抗原,尤其是FT - 1抗原,将成为理解白血病细胞中正常沉默的遗传信息激活机制的有用标志物。总之,对FT抗原进行进一步的生化和遗传分析将有助于理解T细胞的个体发生发育以及T细胞白血病的白血病发生过程。

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