Analysis of the human thymic perivascular space during aging

Analysis of the human thymic perivascular space during aging
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DOI:
10.1172/jci7558
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发表时间:
1999-10-01
影响因子:
15.9
通讯作者:
Hale, LP
Hale, LP
中科院分区:
医学1区
文献类型:
--
作者:
Flores, KG;Li, J;Hale, LP

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人胸腺血管周围空间(PVS)随着胸腺生成功能的下降而增大。因此,了解PVS的组成对于了解胸腺萎缩的机制至关重要。我们分析了87例正常和31例重症肌无力(MG)患者的胸腺组织,年龄从新生儿到78岁,使用免疫组织学和分子检测。我们证实,虽然胸腺上皮间隙(TES)体积随着年龄的增长而逐渐减少,但胸腺生成与活性T细胞受体基因重排在TES内正常持续到晚年。成人PVS中存在的造血细胞包括T细胞、B细胞和单核细胞。嗜酸性粒细胞在2岁或2岁以下婴儿的PVS中突出。在正常成人和MG胸腺中,PVS包括表达CD 45 RO的成熟单阳性(CD 1a(-)和CD 4(+)或CD 8(+))T淋巴细胞,并含有表达TIA-1细胞毒性颗粒抗原的T细胞簇,表明外周起源。PBMC在体外与PVS中存在的MECA-79(+)高内皮微静脉结合,表明外周细胞募集至胸腺PVS的机制。因此,在正常受试者和MG患者中,胸腺PVS可能是外周免疫系统的一个区室,不直接参与胸腺生成。
The perivascular space (PVS) of human thymus increases in volume during aging as thymopoiesis declines. Understanding the composition of the PVS is therefore vital to understanding mechanisms of thymic atrophy. We have analyzed 87 normal and 31 myasthenia gravis (MG) thymus tissues from patients ranging in age from newborn to 78 years, using immunohistologic and molecular assays. We confirmed that although thymic epithelial space (TES) volume decreases progressively with age, thymopoiesis with active T-cell receptor gene rearrangement continued normally within the TES into late life. Hematopoietic cells present in the adult PVS include T cells, B cells, and monocytes. Eosinophils are prominent in PVS of infants 2 years of age or younger. In the normal adult and the MG thymus, the PVS includes mature single-positive (CD1a(-) and CD4(+) or CD8(+))T lymphocytes that express CD45RO, and contains clusters of T cells expressing the TIA-1 cytotoxic granule antigen, suggesting a peripheral origin. PBMCs bind in vitro to MECA-79(+) high endothelial venules present in the PVS, suggesting a mechanism for the recruitment of peripheral cells to thymic PVS. Therefore, in both normal subjects and MG patients, thymic PVS may be a compartment of the peripheral immune system that is not directly involved in thymopoiesis.