Department of Data Science and Engineering, Silesian University of Technology, Gliwice, Poland.
Department of Molecular Biosciences, Radiation Effects Research Foundation, Hiroshima, Japan.
Front Immunol. 2023 Oct 13;14:1224304. doi: 10.3389/fimmu.2023.1224304. eCollection 2023.
The diversity of the antigenic T cell receptor (TCR) repertoire clonally expressed on T lymphocytes is a key element of the adaptive immune system protective functions. A decline in diversity in the older adults is associated with health deterioration. This diversity is generated by the rearrangement of TRB genes coding for TCR chains during lymphocyte differentiation in the thymus, but is essentially maintained by peripheral T lymphocytes proliferation for most of life. Deep sequencing of rearranged TRB genes from blood cells allows the monitoring of peripheral T cell repertoire dynamics. We analysed two aspects of rearranged TRB diversity, related to T lymphocyte proliferation and to the distribution of the T cell clone size, in a collection of repertoires obtained from 1 to 74 years-old donors.
Our results show that peripheral T lymphocytes expansion differs according to the recombination status of their TRB loci. Their proliferation rate changes with age, with different patterns in men and women. T cell clone size becomes more heterogeneous with time, and, in adults, is always more even in women. Importantly, a longitudinal analysis of TRB repertoires obtained at ten years intervals from individual men and women confirms the findings of this cross-sectional study.
Peripheral T lymphocyte proliferation partially depends on their thymic developmental history. The rate of proliferation of T cells differing in their TRB rearrangement status is different in men and women before the age of 18 years old, but similar thereafter.
T 淋巴细胞上克隆表达的抗原 T 细胞受体（TCR）的多样性是适应性免疫系统保护功能的关键要素。老年人多样性的下降与健康恶化有关。这种多样性是由 TRB 基因在胸腺中编码 TCR 链的重排产生的，但在大多数生命中，主要通过外周 T 淋巴细胞增殖来维持。对来自 1 至 74 岁供体的血细胞中重排的 TRB 基因进行深度测序，可监测外周 T 细胞库的动态。我们分析了与 T 淋巴细胞增殖和 T 细胞克隆大小分布相关的两个方面的重排 TRB 多样性，这些方面是从一组库中获得的。
我们的结果表明，外周 T 淋巴细胞的扩增取决于其 TRB 基因座的重组状态。它们的增殖率随年龄而变化，男性和女性的模式不同。T 细胞克隆大小随时间变得更加异质，而且在成年人中，女性的克隆大小总是更加均匀。重要的是，对来自个体男性和女性的 TRB 库进行的十年一次的纵向分析证实了这项横断面研究的发现。
外周 T 淋巴细胞的增殖部分取决于其胸腺发育史。在 18 岁之前，TRB 重排状态不同的 T 细胞的增殖率在男性和女性中存在差异，但此后相似。
