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Effect of age and sex on immune checkpoint expression and kinetics in human T cells
Immunity & Ageing ( IF 7.9 ) Pub Date : 2020-11-04 , DOI: 10.1186/s12979-020-00203-y
Rosanne D. Reitsema , Rebeca Hid Cadena , Sander H. Nijhof , Wayel H. Abdulahad , Minke G. Huitema , Davy Paap , Elisabeth Brouwer , Annemieke M. H. Boots , Peter Heeringa

Immune checkpoints are crucial molecules in maintaining a proper immune balance. Even though age and sex are known to have effects on the immune system, the interplay between age, sex and immune checkpoint expression by T cells is not known. The aim of this study was to determine whether age and sex affect immune checkpoint expression by T cells and if age and sex affect the kinetics of immune checkpoint expression following ex vivo stimulation. In this study, whole blood samples of 20 healthy young adults (YA, 9 males and 11 females) and 20 healthy older adults (OA, 9 males and 11 females) were stained for lymphocyte lineage markers and immune checkpoints and frequencies of CD28+, PD-1+, VISTA+ and CD40L+ T cells were determined. Immune checkpoint expression kinetics were studied following ex vivo anti-CD3/anti-CD28 stimulation of T cells from young and older healthy adults. We report an age-associated increase of CD40L + CD4+ and CD40L + CD8+ T-cell frequencies, whereas CD40+ B-cell frequencies were decreased in older adults, suggesting modulation of the CD40L-CD40 interaction with age. Immune checkpoint expression kinetics revealed differences in magnitude between CD4+ and CD8+ T cells independent of age and sex. Further analysis of CD4+ T-cell subsets revealed an age-associated decrease of especially PD-1 + CD4+ memory T cells which tracked with the female sex. Collectively, our results demonstrate that both age and sex modulate expression of immune checkpoints by human T cells. These findings may have implications for optimising vaccination and immune checkpoint immunotherapy and move the field towards precision medicine in the management of older patient groups.

中文翻译:

年龄和性别对人T细胞免疫检查点表达和动力学的影响

免疫检查点是维持适当免疫平衡的关键分子。尽管已知年龄和性别会对免疫系统产生影响,但尚不清楚年龄,性别和T细胞表达免疫检查点之间的相互作用。这项研究的目的是确定年龄和性别是否会影响T细胞免疫检查点的表达,以及年龄和性别是否会影响离体刺激后免疫检查点表达的动力学。在这项研究中,对20名健康的年轻人(YA,9例男性和11名女性)和20名健康的成年人(OA,9例男性和11女性)的全血样本进行了淋巴细胞谱系标记,免疫检查点和CD28 +,PD频率的染色测定了-1 +,VISTA +和CD40L + T细胞。在对来自年轻和年长健康成年人的T细胞进行离体抗CD3 /抗CD28刺激后,研究了免疫检查点表达动力学。我们报告了与年龄相关的CD40L + CD4 +和CD40L + CD8 + T细胞频率的增加,而CD40 + B细胞频率在老年人中降低,表明CD40L-CD40相互作用随年龄的增长而调节。免疫检查点表达动力学揭示了CD4 +和CD8 + T细胞之间的大小差异,与年龄和性别无关。CD4 + T细胞亚群的进一步分析表明,与年龄相关的尤其是PD-1 + CD4 +记忆T细胞的减少与女性有关。总体而言,我们的研究结果表明,年龄和性别均可调节人T细胞免疫检查点的表达。
更新日期:2020-11-04
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