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衰老小鼠中缺陷的 CD8 T 细胞反应是由于病毒特异性前体的数量和质量变化所致。

Defective CD8 T cell responses in aged mice are due to quantitative and qualitative changes in virus-specific precursors.

机构信息

Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.

出版信息

J Immunol. 2012 Feb 15;188(4):1933-41. doi: 10.4049/jimmunol.1101098. Epub 2012 Jan 13.


DOI:10.4049/jimmunol.1101098
PMID:22246631
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3320034/
Abstract

Aging is associated with suboptimal CD8 T cell responses to viral infections. It is not clear whether these poor responses are due to environmental influences or quantitative and qualitative changes in the pool of responding CD8 T cells. Our studies demonstrated several deleterious age-related changes in the pool of Ag-specific CD8 T cells that respond to infection. The majority of CD8 T cells from uninfected aged mice was CD44(Hi) and had increased expression of inhibitory receptors including PD1, LAG3, 2B4, and CD160. These aged CD44(Hi) CD8 T cells were transcriptionally similar to exhausted CD8 T cells found during chronic infections. In addition, the number of virus-specific precursors in aged mice prior to infection was decreased up to 10-fold, and many of these Ag-specific precursors had high expression of CD44 and PD1. Finally, TCR transgenic studies demonstrated that the CD44(Hi) Ag-specific CD8 T cells from unimmunized aged and young mice were qualitatively inferior compared with CD44(Lo) CD8 T cells from aged or young donors. Thus, a decrease in precursor frequency as well as qualitative changes of CD8 T cells during aging are directly related to impaired immunity.

摘要

衰老是与病毒感染时的 CD8 T 细胞反应不理想相关联的。目前尚不清楚这些不良反应是由于环境影响还是由于应答 CD8 T 细胞池的数量和质量发生了变化。我们的研究表明,在感染过程中,针对抗原的特异性 CD8 T 细胞池中存在几种有害的与年龄相关的变化。来自未感染的老年小鼠的大多数 CD8 T 细胞是 CD44(Hi),并且表达了抑制性受体,包括 PD1、LAG3、2B4 和 CD160。这些老年 CD44(Hi) CD8 T 细胞在转录上与慢性感染期间发现的耗尽的 CD8 T 细胞相似。此外,感染前老年小鼠中病毒特异性前体的数量减少了多达 10 倍,并且许多这些 Ag 特异性前体具有高表达的 CD44 和 PD1。最后,TCR 转基因研究表明,与来自老年或年轻供体的 CD44(Lo) CD8 T 细胞相比,来自未免疫的老年和年轻小鼠的 CD44(Hi) Ag 特异性 CD8 T 细胞在质量上较差。因此,在衰老过程中,前体频率的降低以及 CD8 T 细胞的质量变化与免疫功能受损直接相关。

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Defective CD8 T cell responses in aged mice are due to quantitative and qualitative changes in virus-specific precursors.

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本文引用的文献

[1]
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[2]
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Nat Immunol. 2011-5-29

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