Age-associated parallel increase of Foxp3+CD4+ regulatory and CD44+CD4+ memory T cells in SJL/J mice
Age-associated parallel increase of Foxp3+CD4+ regulatory and CD44+CD4+ memory T cells in SJL/J mice
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DOI：
10.1016/j.cellimm.2009.05.003
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发表时间：
2009-01-01
影响因子：
4.3
通讯作者：
Feng, Ji-Ming
中科院分区：
文献类型：
--
作者：
Han, Guang-Ming;Zhao, Baohua;Feng, Ji-Ming
效应/记忆T细胞（Tem）是维持成功免疫所必需的，而调节性T细胞（Treg）是防止过度/不受控制的炎症和/或自身免疫所必需的。虽然Tern和Treg细胞在衰老过程中都增加，但Foxp 3（+）Treg细胞和CD 44（+）Tern细胞比例增加与衰老之间的关系尚不清楚。本研究发现SJL/J小鼠Foxp 3（+）Treg细胞与CD 44（+）Tem细胞在衰老过程中平行增加，且Foxp 3（+）Treg细胞均为CD 44（+）Tem表型，提示Foxp 3（+）Treg细胞的增加来源于随衰老而扩增的CD 44（+）Tem细胞库。我们的体外动力学研究进一步表明Foxp 3（+）Treg细胞通过CD 44（+）阶段转化。此外，我们观察到，尽管Foxp 3（+）Treg和CD 44（+）Foxp 3（-）Tern细胞之间的平衡随着年龄的增长而保持，但老年小鼠具有更高的Tern和Treg细胞与幼稚T细胞的比率，导致“萎缩的”幼稚T细胞池。我们的研究结果表明，年龄相关的T细胞库的不平衡是一种机制，有助于霍奇金淋巴瘤的自发发生在老年SJL/J小鼠。(C)2009 Elsevier Inc. All rights reserved.
Effector/memory T cells (Tem) are required to maintain successful immunity, while regulatory T cells (Treg) are required to prevent excessive/uncontrolled inflammation and/or autoimmunity. Although both Tern and Treg cells are increased during aging, the relationship between the increased proportion of Foxp3(+) Treg cells and CD44(+) Tern cells with aging is not clearly understood. We found in this report that Foxp3(+) Treg cells are increased in parallel with CD44(+) Tern cells in SJL/J mice with aging, and that all Foxp3(+) Treg cells are of CD44(+) Tem phenotype, suggesting that the increased Foxp3(+) Treg cells originated from the expanded pool of CD44(+) Tem cells with aging. Our in vitro kinetic studies further suggested that Foxp3(+) Treg cells are converted through the CD44(+) stage. Furthermore, we observed that although the balance between Foxp3(+) Treg and CD44(+)Foxp3(-) Tern cells remained with aging, the aged mice have higher ratios of both Tern and Treg cells vs. naive T cells resulting in the "shrunken" naive T cell pools. Our results suggest that an age-associated imbalance of T cell repertoire is a mechanism that contributes to spontaneous occurrence of Hodgkin's-like lymphoma in aged SJL/J mice. (C) 2009 Elsevier Inc. All rights reserved.