Clonal expansions and loss of receptor diversity in the naive CD8 T cell repertoire of aged mice.
Clonal expansions and loss of receptor diversity in the naive CD8 T cell repertoire of aged mice.
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DOI：
10.4049/jimmunol.182.2.784
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发表时间：
2009-01-15
期刊：
影响因子：
--
通讯作者：
Blackman MA
中科院分区：
文献类型：
--
作者：
Ahmed M;Lanzer KG;Yager EJ;Adams PS;Johnson LL;Blackman MA
CD8 T细胞的外周库存在明显的年龄相关变化，其特征是naïve与记忆T细胞的比例降低，以及记忆池中大量克隆扩增的发展。此外，naïve T细胞的TCR库随着年龄的增长而减少。由于naïve T细胞的多样性是对新感染和疫苗接种的有力反应所必需的，因此人们对了解导致库多样性下降的机制非常感兴趣。有人提出，naïve T细胞库多样性下降的一个原因是，在没有新的胸腺移植物来维持naïve外周细胞库的情况下，对稳态增殖的依赖日益增加。在这里，我们通过DNA谱型和序列分析分析了年轻和老年小鼠的naïve CD8 T细胞库。我们的数据表明，与来自年轻小鼠的naïve CD8 T细胞的正常高斯谱型特征相比，老年小鼠的naïve T细胞具有扰动谱型特征。此外，DNA序列分析正式证明了与偏斜谱型相关的多样性损失。出乎意料的是，我们在老年而非年轻小鼠的naïve T细胞中发现了相同序列的多个重复，这与之前仅在记忆T细胞池中描述的克隆扩增一致。naïve T细胞的克隆扩增表明，幼鼠维持naïve T细胞库多样性的正常稳态增殖机制出现了失调。
There are well-characterized age-related changes in the peripheral repertoire of CD8 T cells, characterized by reductions in the ratio of naïve to memory T cells and the development of large clonal expansions in the memory pool. In addition, the TCR repertoire of naïve T cells is reduced with aging. As a diverse repertoire of naïve T cells is essential for a vigorous response to new infections and vaccinations, there is much interest in understanding mechanisms responsible for declining repertoire diversity. It has been proposed that one reason for declining repertoire diversity in the naïve T cell pool is an increasing dependence on homeostatic proliferation in the absence of new thymic emigrants for maintenance of the naïve peripheral pool. Here we have analyzed the naïve CD8 T cell repertoire in young and aged mice by DNA spectratype and sequence analysis. Our data show that naïve T cells from aged mice have perturbed spectratype profiles compared to the normally Gaussian spectratype profiles characteristic of naïve CD8 T cells from young mice. In addition, DNA sequence analysis formally demonstrated a loss of diversity associated with skewed spectratype profiles. Unexpectedly, we found multiple repeats of the same sequence in naïve T cells from aged but not young mice, consistent with clonal expansions previously described only in the memory T cell pool. Clonal expansions among naïve T cells suggests dysregulation in the normal homeostatic proliferative mechanisms that operate in young mice to maintain diversity in the naïve T cell repertoire.
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影响因子：
32.4
作者：
Ernst, B;Lee, DS;Surh, CD
通讯作者：
Surh, CD
胸腺和最近的胸腺移民在维持成年外周淋巴细胞库中的作用。
影响因子：
15.3
作者：
Berzins, S P;Boyd, R L;Miller, J F
通讯作者：
Miller, J F
影响因子：
20.3
作者：
Bacsi, S;De Palma, R;Aster, RH
通讯作者：
Aster, RH
DOI：
10.1016/0167-5699(96)80543-3
发表时间：
1996-06-01
期刊：
IMMUNOLOGY TODAY
影响因子：
--
作者：
George, AJT;Ritter, MA
通讯作者：
Ritter, MA
DOI：
10.1016/0192-0561(92)90115-2
发表时间：
1992-05-01
期刊：
INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY
影响因子：
--
作者：
GREENSTEIN, BD;DEBRIDGES, EF;FITZPATRICK, FTA
通讯作者：
FITZPATRICK, FTA