Cell proliferation and differentiation in the fetal and early postnatal mouse thymus.

Cell proliferation and differentiation in the fetal and early postnatal mouse thymus.
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DOI:
10.4049/jimmunol.142.10.3369
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发表时间:
1989-05
影响因子:
4.4
通讯作者:
C. Pénit;F. Vasseur
C. Pénit;F. Vasseur
中科院分区:
医学2区
文献类型:
--
作者:
C. Pénit;F. Vasseur

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通过用溴脱氧尿苷标记DNA合成胸腺细胞并用抗CD 4、CD 8、J11 d、吞噬糖蛋白1、TCR V β 8链、Thy-1和IL-2 R表面蛋白的抗体染色,研究了胸腺个体发育过程中细胞增殖和细胞分化之间的关系。胸腺的发育是不连续的,从胎龄13天至18天和出生后3天至6天有两个明确的生长期,从第8天至2周有更多的进行性生长。细胞增殖开始于胎龄12天,即造血干细胞到达第三鳃囊后1天。这些细胞吞噬糖蛋白1阳性,但IL-2 R和Thy-1阴性。因此,细胞增殖先于IL-2 R表达。直到第15天,CD 4 -8-胸腺细胞扩增而不分化。然后出现CD 4 -8+和CD 4 +8+细胞;这种诱导是增殖依赖性的,并且发生在已经失去IL-2 R的细胞上,但就在该受体的最大表达之后。在几天内,胸腺保持恒定的大小(约10(7)个细胞),表现与稳态胸腺相似。出生后第3天,扩增再次开始,并与CD 4 -8增殖指数和IL-2 R表达的增加相关。与此同时,胸腺亚群能够扩增而不分化,再次,短暂,可检测。这些结果表明,流入胸腺的前体细胞是永久性的,但在个体发育过程中的几个时间短暂增加。此外,胎儿CD 4 -8-细胞的行为似乎与成人前体细胞的行为没有根本的不同,但实际的差异在于不同成熟阶段的CD 4 -8-细胞的相对比例的变化,如通过循环细胞的IL-2 R表达的显著变化所揭示的。
The relationships between cell proliferation and cell differentiation during thymus ontogeny were studied by labeling DNA-synthesizing thymocytes with bromodeoxyuridine and staining with antibodies against CD4, CD8, J11d, phagocytic glycoprotein 1, TCR V beta 8 chain, Thy-1, and IL-2R surface proteins. The development of the thymus was discontinuous, with two well defined growth periods from 13 days to 18 days of fetal life and from 3 days to 6 days after birth, and more progressive growth from day 8 to 2 wk. Cell proliferation started on fetal day 12, 1 day after the arrival of hemopoietic stem cells in the third branchial pouch. These cells were phagocytic glycoprotein 1-positive but IL-2R and Thy-1 negative. Thus, cell proliferation preceded IL-2R expression. Until day 15, CD4-8- thymocytes expanded without differentiation. Then CD4-8+ and CD4+8+ cells appeared; this induction was proliferation dependent and occurred on cells which had already lost IL-2R, but just after maximum expression of this receptor. During several days, the thymus remained of constant size (around 10(7) cells) and behaved like the steady state thymus. On day 3 after birth, expansion started again and was correlated with an increase in CD4-8- proliferation index and IL-2R expression. At the same time, the thymic subset capable of expansion without differentiation was again, transiently, detectable. These results suggest that the inflow of precursor cells into the thymus is permanent but transiently increased at several times during ontogeny. Moreover, the behavior of fetal CD4-8- cells does not appear radically different from that of adult precursors, but the actual difference resides in the variation of the relative proportion of CD4-8- cells at different maturation stages, as revealed by striking variations of IL-2R expression by cycling cells.