Kurashima C, Utsuyama M, Kasai M, Ishijima S A, Konno A, Hirokawa K
Department of Pathology, Tokyo Metropolitan Institute of Gerontology, Japan.
Int Immunol. 1995 Jan;7(1):97-104. doi: 10.1093/intimm/7.1.97.
Mouse CD4+ T cells were subdivided into two subpopulations, naive (CD44low CD45RBhigh) and memory (CD44high CD45RBlow) T cells, by flow cytometric analysis. Examination of spleen and peripheral blood of C57BL/6 mice of various ages revealed that there was a reciprocal age-associated change in these two subpopulations, i.e. naive T cells predominant in young mice decreased with age, while memory T cells increased. In order to investigate the role of the thymus in the age change of naive and memory T cells, we employed two experimental systems: radiation bone marrow chimeras constructed between young and old mice, and grafting of young or old thymus into nude mice. Data from these two experiments suggested that the young thymus has a greater ability to provide naive T cells than the old thymus, while the old thymus favors the maintenance of memory T cells rather than naive T cells. In reference to cytokine production by enriched naive and memory T cells, young naive T cells produced mainly IL-2 and young memory T cells mainly IL-4. On the other hand, in old mice, memory T cells produced twice as much IL-2 than naive T cells, although the level was significantly lower than that of young mice. In addition, old naive T cells produced twice as much IL-4 than old memory T cells. These results suggested a distinct age change in the profile of cytokine production and functional heterogeneity of two Th cell subpopulations.
通过流式细胞术分析，将小鼠CD4⁺ T细胞细分为两个亚群，即初始（CD44low CD45RBhigh）T细胞和记忆（CD44high CD45RBlow）T细胞。对不同年龄的C57BL/6小鼠的脾脏和外周血进行检测发现，这两个亚群存在与年龄相关的相反变化，即幼鼠中占主导的初始T细胞随年龄增长而减少，而记忆T细胞则增加。为了研究胸腺在初始T细胞和记忆T细胞年龄变化中的作用，我们采用了两个实验系统：在年轻和年老小鼠之间构建辐射骨髓嵌合体，以及将年轻或年老的胸腺移植到裸鼠体内。这两个实验的数据表明，年轻胸腺比年老胸腺有更强的提供初始T细胞的能力，而年老胸腺更有利于记忆T细胞而非初始T细胞的维持。关于富集的初始T细胞和记忆T细胞产生的细胞因子，年轻的初始T细胞主要产生IL-2，年轻的记忆T细胞主要产生IL-4。另一方面，在老年小鼠中，记忆T细胞产生的IL-2是初始T细胞的两倍，尽管其水平明显低于年轻小鼠。此外，老年初始T细胞产生的IL-4是老年记忆T细胞的两倍。这些结果表明，两个Th细胞亚群在细胞因子产生谱和功能异质性方面存在明显的年龄变化。
