Homeostasis of the naive CD4+ T cell compartment, during aging
Homeostasis of the naive CD4+ T cell compartment, during aging
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DOI：
10.4049/jimmunol.180.3.1499
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发表时间：
2008-02-01
影响因子：
4.4
通讯作者：
Jamieson, Beth D.
中科院分区：
文献类型：
--
作者：
Kilpatrick, Ryan D.;Rickabaugh, Tammy;Jamieson, Beth D.
尽管胸腺退化，但初始CD 4（+）T细胞的数量在衰老过程中缓慢减少，这表明这些细胞在外周血中有相当大的稳态扩增。为了研究初始CD 4（+）T细胞稳态的机制和后果，我们评估了初始CD 4（+）T细胞亚群CD 45 RA（+）CD 31（+）和CD 45 RA（+）CD 31（-）的年龄依赖性动力学。采用横断面和纵向研究设计，我们测量了22至73岁个体中两个亚群的相对比例，并量化了这些亚群中TCR切除环的含量，作为增殖史的指标。我们的研究结果表明，随着时间的推移，胸腺输出减少导致CD 45 RA（+）CD 31（+）幼稚CD 4 + T细胞减少，尽管我们注意到这种变化的动力学存在相当大的个体差异。相反，由于广泛的外周增殖，CD 45 RA（+）CD 31（-）幼稚CD 4（+）T细胞亚群没有显著下降。我们的纵向数据首次证明，CD 45 RA（+）CD 31（+）CD 4（+）亚群也经历了一些体内增殖，而不会立即损失CD 31，导致CD 45 RA（+）CD 31（+）增殖后代的积累。衰老与两个亚群中的端粒缩短有关，增加了增殖后代的积累有助于老年人幼稚CD 4（+）T细胞区室衰老的可能性。相反，我们观察到尽管外周扩增，但克隆TCR多样性保持不变，尽管该分析不包括65岁以上的个体。我们的研究结果提供了对衰老过程中幼稚CD 4 + T细胞稳态的深入了解，可用于更好地理解可能有助于该隔室内免疫衰老的机制。
Despite thymic involution, the number of naive CD4(+) T cells diminishes slowly during aging, suggesting considerable peripheral homeostatic expansion of these cells. To investigate the mechanisms behind, and consequences of, naive CD4(+) T cell homeostasis, we evaluated the age-dependent dynamics of the naive CD4(+) T cell subsets CD45RA(+)CD31(+) and CD45RA(+)CD31(-). Using both a cross-sectional and longitudinal study design, we measured the relative proportion of both subsets in individuals ranging from 22 to 73 years of age and quantified TCR excision circle content within those subsets as an indicator of proliferative history. Our findings demonstrate that waning thymic output results in a decrease in CD45RA(+)CD31(+) naive CD4+ T cells over time, although we noted considerable individual variability in the kinetics of this change. In contrast, there was no significant decline in the CD45RA(+)CD31(-) naive CD4(+) T cell subset due to extensive peripheral proliferation. Our longitudinal data are the first to demonstrate that the CD45RA(+)CD31(+)CD4(+) subset also undergoes some in vivo proliferation without immediate loss of CD31, resulting in an accumulation of CD45RA(+)CD31(+) proliferative offspring. Aging was associated with telomere shortening within both subsets, raising the possibility that accumulation of proliferative offspring contributes to senescence of the naive CD4(+) T cell compartment in the elderly. In contrast, we observed retention of clonal TCR diversity despite peripheral expansion, although this analysis did not include individuals over 65 years of age. Our results provide insight into naive CD4+ T cell homeostasis during aging that can be used to better understand the mechanisms that may contribute to immunosenescence within this compartment.