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随着 T 细胞受体: pMHC 相互作用的影响,幼稚 CD8+ T 细胞库的非随机耗竭与衰老有关。

Nonrandom attrition of the naive CD8+ T-cell pool with aging governed by T-cell receptor:pMHC interactions.

机构信息

Department of Immunobiology and the Arizona Center on Aging, University of Arizona College of Medicine, Tucson, AZ 85724, USA.

出版信息

Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13694-9. doi: 10.1073/pnas.1107594108. Epub 2011 Aug 3.

Abstract

Immunity against new infections declines in the last quartile of life, as do numbers of naive T cells. Peripheral maintenance of naive T cells over the lifespan is necessary because their production drastically declines by puberty, a result of thymic involution. We report that this maintenance is not random in advanced aging. As numbers and diversity of naive CD8(+) T cells declined with aging, surviving cells underwent faster rates of homeostatic proliferation, were selected for high T-cell receptor:pMHC avidity, and preferentially acquired "memory-like" phenotype. These high-avidity precursors preferentially responded to infection and exhibited strong antimicrobial function. Thus, T-cell receptor avidity for self-pMHC provides a proofreading mechanism to maintain some of the fittest T cells in the otherwise crumbling naive repertoire, providing a degree of compensation for numerical and diversity defects in old T cells.

摘要

随着生命的最后一个季度的到来,新感染的免疫力下降,以及幼稚 T 细胞的数量也会下降。为了维持外周血中幼稚 T 细胞的数量,需要使其在整个生命周期中保持稳定,因为青春期时胸腺的退化导致幼稚 T 细胞的产生急剧下降。我们报告说,在衰老过程中,这种维持不是随机的。随着幼稚 CD8(+)T 细胞数量和多样性随年龄增长而下降,存活的细胞经历了更快的同源性增殖,被选择具有高 T 细胞受体:pMHC 亲和力,并优先获得“记忆样”表型。这些高亲和力的前体细胞优先对感染作出反应,并表现出强大的抗菌功能。因此,T 细胞受体对自身 pMHC 的亲和力为维持幼稚 T 细胞库中适应性最强的部分提供了一种校对机制,为老年 T 细胞数量和多样性缺陷提供了一定程度的补偿。

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