Han Guang-Ming, Zhao Baohua, Jeyaseelan Samithamby, Feng Ji-Ming
Department of Comparative Biomedical Sciences, Louisiana State University, Baton Rouge, 70803, USA.
Cell Immunol. 2009;258(2):188-96. doi: 10.1016/j.cellimm.2009.05.003. Epub 2009 May 18.
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 Tem and Treg cells are increased during aging, the relationship between the increased proportion of Foxp3(+) Treg cells and CD44(+) Tem cells with aging is not clearly understood. We found in this report that Foxp3(+) Treg cells are increased in parallel with CD44(+) Tem 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(-) Tem cells remained with aging, the aged mice have higher ratios of both Tem and Treg cells vs. naïve T cells resulting in the "shrunken" naïve 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.
效应/记忆性T细胞（Tem）对于维持成功的免疫反应是必需的，而调节性T细胞（Treg）对于预防过度/失控的炎症和/或自身免疫是必需的。尽管Tem细胞和Treg细胞在衰老过程中都会增加，但Foxp3(+) Treg细胞和CD44(+) Tem细胞比例增加与衰老之间的关系尚不清楚。我们在本报告中发现，在衰老的SJL/J小鼠中，Foxp3(+) Treg细胞与CD44(+) Tem细胞同时增加，并且所有Foxp3(+) Treg细胞都具有CD44(+) Tem表型，这表明随着衰老，增加的Foxp3(+) Treg细胞源自CD44(+) Tem细胞的扩增池。我们的体外动力学研究进一步表明，Foxp3(+) Treg细胞是通过CD44(+)阶段转化而来的。此外，我们观察到，尽管随着衰老，Foxp3(+) Treg细胞和CD44(+)Foxp3(-) Tem细胞之间的平衡得以维持，但老年小鼠的Tem细胞和Treg细胞与幼稚T细胞的比例均更高，导致幼稚T细胞池“缩小”。我们的结果表明，与年龄相关的T细胞库失衡是导致老年SJL/J小鼠自发发生霍奇金样淋巴瘤的一种机制。
