Vicente A, Varas A, Sacedón R, Zapata A G
Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain.
Anat Rec. 1996 Apr;244(4):506-19. doi: 10.1002/(SICI)1097-0185(199604)244:4<506::AID-AR9>3.0.CO;2-S.
Despite the assumed importance of thymic cell microenvironments for governing T-cell maturation, little is known about the ontogeny of their cell components. A few studies have analyzed previously the ontogenetical development of rat thymic epithelium (Bogojevic et al. 1990. Period. Biol., 92:126; Kampinga and Aspinall 1990 Harwood Acad. Pub., London, pp. 149-186; Micic et al., 1991 Dev. Comp. Immunol., 15:443-450) and recently we have reported the development of both interdigitating/dendritic cells and macrophages (Vicente et al., 1994 Immunology, 82:75-81, 1995 Immunology, 85:99-105).
In the present work we analyze in situ ultrastructural, immunohistochemical, and histoenzymatically the appearance and development of the thymic epithelial cell component in both embryonic and neonatal Wistar rats with special emphasis on the origin of the different epithelial cell types, the occurrence or absence of a common precursor for these, and the expression of MHC molecules.
The thymic primordium of 13-day-old embryos is formed by a homogeneous population of primitive epithelial cells differentiating gradually into various epithelial cell subtypes of both the cortex and the medulla. In the cortex, subcapsular and stroma-supporting epithelial cells appear at days 14-15 as two structurally different cell entities. At the same time, stroma-supporting, keratinized, and vacuolated epithelial cells occur in the thymic medulla. These last two cell types differentiate subsequently into Hassall's bodies and hypertrophied cells. Lympho-epithelial cell complexes are identified in the deep cortex around birth, when the cortical parenchyma houses a transitional erythropoiesis. mAbs (His-39, RMC-20) which recognize medullary epithelial cells in the adult thymus stain positively cells of the thymic primordium as early as day 16 of embryonic life. Cortical epithelial cell markers (His-37, RMC-17) appear, however, slightly later and the subcapsulary region is not established until postnatal life. MHC class I and class II molecules can be identified on epithelial cells in the thymus of 15-day-old embryonic rats although they reach the highest expression around birth.
Our results confirm the heterogeneity of the thymic epithelial component, the persistence of primitive, non-differentiated epithelial cells morphologically similar to those occurring in the early thymic primordium in adult thymus, and the mutual relevance of epithelial cells and thymocytes for an adequate development of rat thymus gland.
尽管胸腺细胞微环境对T细胞成熟的重要性已得到公认,但对其细胞成分的个体发生却知之甚少。此前已有一些研究分析了大鼠胸腺上皮的个体发生发育情况(Bogojevic等人,1990年,《生物学通报》,92:126;Kampinga和Aspinall,1990年,哈伍德学术出版社,伦敦,第149 - 186页;Micic等人,1991年,《发育与比较免疫学》,15:443 - 450),最近我们报道了交错突/树突状细胞和巨噬细胞的发育情况(Vicente等人,1994年,《免疫学》,82:75 - 81,1995年,《免疫学》,85:99 - 105)。
在本研究中,我们通过原位超微结构、免疫组织化学和组织酶学方法,分析了胚胎期和新生期Wistar大鼠胸腺上皮细胞成分的出现和发育情况,特别关注不同上皮细胞类型的起源、它们是否存在共同前体以及MHC分子的表达。
13日龄胚胎的胸腺原基由一群均匀的原始上皮细胞组成,这些细胞逐渐分化为皮质和髓质的各种上皮细胞亚型。在皮质中,被膜下和支持基质的上皮细胞在第14 - 15天出现,为两种结构不同的细胞实体。同时,支持基质、角化和空泡化的上皮细胞出现在胸腺髓质中。后两种细胞类型随后分化为哈氏小体和肥大细胞。出生前后,在深部皮质中可识别出淋巴细胞 - 上皮细胞复合体,此时皮质实质内存在过渡性红细胞生成。识别成年胸腺中髓质上皮细胞的单克隆抗体(His - 39,RMC - 20)早在胚胎期第16天就能使胸腺原基的细胞呈阳性染色。然而,皮质上皮细胞标志物(His - 37,RMC - 17)出现稍晚,被膜下区域直到出生后才形成。15日龄胚胎大鼠胸腺的上皮细胞上可识别出MHC I类和II类分子,尽管它们在出生前后达到最高表达。
我们的结果证实了胸腺上皮成分的异质性、形态上类似于早期胸腺原基中细胞的原始未分化上皮细胞在成年胸腺中的持续存在,以及上皮细胞和胸腺细胞对于大鼠胸腺正常发育的相互关联性。