Patterns of cytokine gene expression by CD4+ T cells from young and old mice.
Patterns of cytokine gene expression by CD4+ T cells from young and old mice.
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DOI：
10.4049/jimmunol.150.8.3602
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发表时间：
1993-04
影响因子：
4.4
通讯作者：
M. Hobbs;W. Weigle;D. Noonan;B. Torbett;R. Mcevilly;Rick Koch;G. Cardenas;D. Ernst
中科院分区：
文献类型：
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作者：
M. Hobbs;W. Weigle;D. Noonan;B. Torbett;R. Mcevilly;Rick Koch;G. Cardenas;D. Ernst
我们已经分析了诱导的细胞因子基因表达和细胞周期活性的模式从小鼠的CD 4+细胞，并研究了这些响应模式如何在衰老过程中的变化。从年轻成年和老年C57 BL/6 NNia小鼠的脾脏中分离CD 4+细胞，并在体外用板结合的抗CD 3 mAb刺激。然后随时间评估细胞积累IL-1 α、IL-1 β、IL-2、IL-3、IL-4、IL-5、IL-6、IFN-γ、TNF-α和TNF-β的转录物;分泌IL-2、IL-3、IL-4、IL-5、IL-6和IFN-γ;以及通过S期进展的能力。在培养物中第一次主要细胞分裂之前（< 32 h），老年组的刺激的CD 4+细胞相对于年轻成人对照含有相似的IL-2、TNF-α和TNF-β转录物峰值水平，而IL-3、IL-4、IL-5和IFN-γ转录物在老年组中积累到显著更高的峰值水平。这些发现与培养后期（24至72小时）细胞因子分泌模式一致：不同年龄组的IL-2峰值水平相似，但老年组释放IL-3、IL-4、IL-5和IFN-γ的能力增强。相比之下，年轻组的CD 4+细胞在细胞分裂前的管家基因rpL 32的超表达和在整个3天培养物中的S期活性水平方面是上级的。对中等年龄小鼠的CD 4+细胞进行的类似分析表明，细胞因子谱的改变从青年到老年逐渐发生，而增殖能力的降低是晚年的变化。与以前的报告一致，我们发现脾CD 4+细胞组也经历了一个渐进的，年龄依赖性的细胞表达高水平的膜CD 44（与记忆或效应细胞相关的表型）的比例增加。此外，通过分离的CD 4 + CD 44 lo和CD 4 + CD 44 hi细胞的IL-3、IL-5和IFN-γ产生的分析显示，产生这些细胞因子的能力主要与CD 44 hi亚群分离，而与供体年龄无关。两者合计，我们的数据表明，逐渐年龄相关的转变，在亚组组成的脾CD 4+细胞池的基础上进行性变化的细胞因子基因表达的模式，由这个细胞群。
We have analyzed the patterns of induced cytokine gene expression and cell cycle activity by CD4+ cells from mice, and have examined how these response patterns change during the aging process. CD4+ cells were isolated from spleens of young adult and old C57BL/6NNia mice and were stimulated in vitro with plate-bound anti-CD3 epsilon mAb. The cells were then assessed over time for the capacity to accumulate transcripts for IL-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IFN-gamma, TNF-alpha, and TNF-beta; to secrete IL-2, IL-3, IL-4, IL-5, IL-6, and IFN-gamma; and to progress through S phase. Before the first major cell division in culture (< 32 h), stimulated CD4+ cells of the old group contained similar peak levels of IL-2, TNF-alpha, and TNF-beta transcripts relative to young adult controls, whereas IL-3, IL-4, IL-5, and IFN-gamma transcripts accumulated to significantly higher peak levels in the old group. These findings were consistent with the patterns of cytokine secretion later in culture (24 to 72 h): the peak IL-2 levels were similar between age groups, but the old group exhibited an enhanced capacity to release IL-3, IL-4, IL-5, and IFN-gamma. In contrast, CD4+ cells of the young group were superior in the hyper-expression of the housekeeping gene, rpL32, before cell division and in the levels of S phase activity throughout 3-day cultures. Similar analyses of CD4+ cells from mice of intermediate ages showed that the alterations in cytokine profiles occurred gradually from young adulthood to old age, whereas the reductions in proliferative capacity were late life changes. Consistent with previous reports, we found that the splenic CD4+ cell group also underwent a progressive, age-dependent increase in the proportions of cells expressing high levels of membrane CD44 (a phenotype associated with memory or effector cells). Moreover, the analysis of IL-3, IL-5, and IFN-gamma production by isolated CD4+CD44lo and CD4+CD44hi cells revealed that the capacity to produce these cytokines segregated predominantly with the CD44hi subset, regardless of donor age. Taken together, our data suggest that gradual age-associated shifts in the subset composition of the splenic CD4+ cell pool underlie progressive changes in the patterns of cytokine gene expression by this cell group.