Thymocytopoiesis is maintained by blood-borne precursors throughout postnatal life. A study in parabiotic mice.
Thymocytopoiesis is maintained by blood-borne precursors throughout postnatal life. A study in parabiotic mice.
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DOI：
10.4049/jimmunol.148.6.1604
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发表时间：
1992-03
影响因子：
4.4
通讯作者：
E. Donskoy;I. Goldschneider
中科院分区：
文献类型：
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作者：
E. Donskoy;I. Goldschneider
本研究旨在解决长期存在的争议，即血液前体或常驻胸腺内前体是否在出生后维持胸腺细胞生成。在21周的时间内，研究了105对未辐照的thy -1异体抗原异种共生B10的胸腺嵌合动力学。老鼠。异种结合6 - 7周后，Thy-1b和Thy-1a的胸腺嵌合达到最高水平，分别为25%和16%（平均分别为20.5%和9.8%）。大多数供体源性胸腺细胞位于胸腺皮层，表达高水平的Thy-1 Ag和末端脱氧核苷酸转移酶。胸腺嵌合没有达到50%，因为循环的胸腺原细胞不像外周T细胞那样在异种伴侣的血液中随机分布。这在辐照的thy -1异体抗原相同的异种共生小鼠中得到了证明，其中一只小鼠被静脉注射了thy -1异体抗原不同的骨髓细胞。72小时后，在相反的对照中仅检测到供体源性胸腺原细胞活性的10%。同样，胸腺嵌合水平在未辐照的、thy -1异体抗原不同的配对体中密切对应于供体：血液中胸腺原细胞的宿主比例（即，在10%到20%之间），直接由胸腺内过继转移试验确定。胸腺嵌合对血源性前体的持续依赖性在异种共生9周后通过手术分离小鼠得到了正式证实。12周后，分离对照组的胸腺嵌合率比假手术对照组低50% - 80%。异种共生和非异种共生小鼠胸腺细胞生成（包括胸腺退化）相似动力学的存在，排除了“应激”在异种共生期间启动或维持胸腺嵌合的可能作用；并且在肾上腺切除和未肾上腺切除的异种共生小鼠中胸腺嵌合的水平相似。因此，这些实验表明，在出生后的生活中，胸腺细胞生成的维持与产前生活一样，主要依赖于血源性胸腺原细胞，胸腺内的前体以平均2 - 3%/天的速度被替换。
This study was designed to resolve the long standing controversy as to whether hematogenous precursors or resident intrathymic precursors maintain thymocytopoiesis in postnatal life. The kinetics of thymic chimerism was examined over a 21-wk period in 105 pairs of nonirradiated, Thy-1-alloantigen-disparate, parabiotic B10.S mice. Thymic chimerism reached reached maximum levels of 25% in the Thy-1b and 16% in the Thy-1a partners (mean 20.5% and 9.8%, respectively) 6 to 7 wk after parabiotic union. Most of the donor-origin thymocytes were located in the thymus cortex and expressed high levels of Thy-1 Ag and terminal deoxynucleotidyl transferase. Thymic chimerism did not reach 50% because circulating prothymocytes, unlike peripheral T cells, do not distribute randomly in the blood of parabiotic partners. This was shown in irradiated pairs of Thy-1-alloantigen-identical parabiotic mice, one member of which was injected i.v. with Thy-1-alloantigen-disparate bone marrow cells. Only 10% of the total donor-origin prothymocyte activity was detected in the opposite parabiont 72 h later. Similarly, the level of thymic chimerism in nonirradiated, Thy-1-alloantigen-disparate parabionts closely corresponded to the donor: host ratio of prothymocytes in the blood (i.e., between 10 and 20%), as determined directly by an intrathymic adoptive transfer assay. The continued dependence of thymic chimerism on blood-borne precursors was formally demonstrated by surgically separating mice 9 wk after parabiosis. Twelve weeks later, thymic chimerism was 50 to 80% lower in the separated parabionts than in sham-operated controls. The possible role of "stress" in initiating or maintaining thymic chimerism during parabiosis appeared to be excluded by the existence of similar kinetics of thymocytopoiesis (including the onset of thymic involution) in parabiotic and nonparabiotic mice; and by the occurrence of similar levels of thymic chimerism in adrenalectomized and nonadrenalectomized parabiotic mice. Thus these experiments demonstrate that the maintenance of thymocytopoiesis in postnatal life, as in prenatal life, is primarily dependent upon blood-borne prothymocytes, and that intrathymic precursors are replaced at an average rate of 2 to 3%/day.