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人类急性运动诱导外周血 T 细胞衰老表型和端粒长度。

Senescent phenotypes and telomere lengths of peripheral blood T-cells mobilized by acute exercise in humans.

机构信息

Laboratory of Integrated Physiology, Department of Health and Human Performance, University of Houston, 3855 Holman Street, Houston, Texas 77204, USA.

出版信息

Exerc Immunol Rev. 2010;16:40-55.

Abstract

Acute bouts of aerobic exercise are known to mobilize antigen-experienced CD8+ T-cells expressing the cell surface marker of senescence, KLRG1, into the blood. It is not known; however if this is due to a selective mobilization of terminally differentiated T-cells (i.e., KLRG1 +/CD28-/CD57+) or a population of effector memory T-cells (i.e., KLRG1+/CD28+/CD57-) that have not reached terminal differentiation. The aim of this study was to further characterize KLRG1 + T-cells mobilized by acute exercise by assessing the co-expression of KLRG1 with CD28 or CD57 and to determine telomere lengths in the CD4+ and CD8+ T-cell subsets. Nine moderately trained male subjects completed an exhaustive treadmill running protocol at 80%. Blood lymphocytes isolated before, immediately after and 1h after exercise were labelled with antibodies against KLRG1, CD28 or CD57, CD4 or CD8 and CD3 for 4-color flow cytometry analysis. Telomere lengths in CD3+, CD4+ and CD8+ T-cells were determined using Q-PCR. The relative proportion of KLRG1 + cells among the CD8+ T-cells increased by 40% immediately after exercise, returning to baseline 1h later. This was due to a mobilization of KLRG1+/CD28- (61% increase), KLRG1+/CD57+ (56% increase) and to a lesser extent, KLRG1+/CD57- cells (24% increase). Telomeres in CD8+ T-cells displayed an increased relative length immediately after exercise, whereas no change occurred for CD4+ or the overall CD3+ T-cells. In conclusion, the increased frequency of KLRG1 +/CD8+ T-cells in blood after acute exercise is predominantly due to a selective mobilization of terminally differentiated T-cells. The increased relative telomere length in CD8+ T-cells after exercise might indicate that KLRG1+ cells mobilized by exercise are under stress or aberrant signaling-induced senescence (STASIS). We postulate that a frequent mobilization of these cells by acute exercise might eventually allow naïve T-cells to occupy the "vacant" immune space and increase the naïve T-cell repertoire.

摘要

急性有氧运动已知会动员表达衰老细胞表面标志物 KLRG1 的抗原经验 CD8+T 细胞进入血液。然而,目前尚不清楚这是由于终末分化 T 细胞(即 KLRG1+/CD28-/CD57+)的选择性动员,还是尚未达到终末分化的效应记忆 T 细胞(即 KLRG1+/CD28+/CD57+)的动员。本研究的目的是通过评估 KLRG1 与 CD28 或 CD57 的共表达来进一步描述急性运动动员的 KLRG1+T 细胞,并确定 CD4+和 CD8+T 细胞亚群中的端粒长度。9 名中等训练的男性受试者在 80%的跑步机上进行了一次耗竭性跑步试验。运动前、运动后立即和运动后 1 小时采集血淋巴细胞,用 KLRG1、CD28 或 CD57、CD4 或 CD8 和 CD3 抗体标记,进行 4 色流式细胞术分析。使用 Q-PCR 测定 CD3+、CD4+和 CD8+T 细胞中的端粒长度。运动后立即,CD8+T 细胞中 KLRG1+细胞的相对比例增加了 40%,1 小时后恢复到基线。这是由于 KLRG1+/CD28-(增加 61%)、KLRG1+/CD57+(增加 56%)和 KLRG1+/CD57-细胞(增加 24%)的动员所致。运动后 CD8+T 细胞中的端粒显示相对长度增加,而 CD4+或总 CD3+T 细胞没有变化。总之,急性运动后血液中 KLRG1+/CD8+T 细胞的频率增加主要是由于终末分化 T 细胞的选择性动员。运动后 CD8+T 细胞中的相对端粒长度增加可能表明运动动员的 KLRG1+细胞处于应激或异常信号诱导的衰老(STASIS)状态。我们推测,急性运动频繁动员这些细胞最终可能使幼稚 T 细胞占据“空缺”的免疫空间并增加幼稚 T 细胞 repertoire。

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