Lymphohematopoietic progenitors do not have a synchronized defect with age-related thymic involution
Lymphohematopoietic progenitors do not have a synchronized defect with age-related thymic involution
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DOI：
10.1111/j.1474-9726.2007.00325.x
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发表时间：
2007-10-01
期刊：
影响因子：
7.8
通讯作者：
Su, Dong-Ming
中科院分区：
文献类型：
--
作者：
Zhu, Xike;Gui, Jingang;Su, Dong-Ming
据推测，老化的淋巴造血祖细胞（LPC），包括造血干细胞（HSC）和早期T细胞祖细胞（ETP）具有内在缺陷，触发年龄相关的胸腺退化。然而，使用不同的方法，我们认为情况并非如此。我们通过将胎儿胸腺移植到老年动物的肾囊中，为老年小鼠提供了一个年轻的胸腺微环境，并证明老年小鼠来源的LPC可以重建正常的胸腺淋巴细胞生成和所有胸腺细胞亚群，包括ETP、双阴性亚群、双阳性和CD 4（+）和CD 8（+）单阳性T细胞。老年小鼠来源的LPCs可通过相互作用改变年轻RAG（-/-）胸腺结构，并提高老年小鼠外周血CD 4（+）IL-2（+）T细胞对共刺激分子的应答率。相反，胸腺内注射的ETP从年轻的动物到老年小鼠分类没有恢复正常的胸腺淋巴细胞生成，这意味着在老年胸腺ETP的短缺和/或缺陷不占与年龄相关的胸腺退化。总之，我们的研究结果表明，与年龄相关的胸腺退化的根本原因主要是胸腺微环境的变化，导致外在的，而不是内在的，T淋巴细胞祖细胞的缺陷。
It has been speculated that aging lymphohematopoietic progenitor cells (LPC) including hematopoietic stem cells (HSC) and early T-cell progenitors (ETP) have intrinsic defects that trigger age-related thymic involution. However, using a different approach, we suggest that that is not the case. We provided a young thymic microenvironment to aged mice by transplanting a fetal thymus into the kidney capsule of aged animals, and demonstrated that old mouse-derived LPCs could re-establish normal thymic lymphopoiesis and all thymocyte subpopulations, including ETPs, double negative subsets, double positive, and CD4(+) and CD8(+) single positive T cells. LPCs derived from aged mice could turn over young RAG(-/-) thymic architecture by interactions, as well as elevate percentage of peripheral CD4(+)IL-2(+) T cells in response to costimulator in aged mice. Conversely, intrathymic injection of ETPs sorted from young animals into old mice did not restore normal thymic lymphopoiesis, implying that a shortage and/or defect of ETPs in aged thymus do not account for age-related thymic involution. Together, our findings suggest that the underlying cause of age-related thymic involution results primarily from changes in the thymic microenvironment, causing extrinsic, rather than intrinsic, defects in T-lymphocyte progenitors.