Publication Date

2019-08-06

Document Type

Article

Disciplines

Immunology and Infectious Disease

Abstract

T-cell memory to pathogens can be envisioned as a receptor-based imprint of the pathogenic environment on the naive repertoire of clonotypes. Recurrent exposures to a pathogen inform and reinforce memory, leading to a mature state. The complexity and temporal stability of this system in man is only beginning to be adequately described. We have been using a rank-frequency approach for quantitative analysis of CD8 T cell repertoires. Rank acts as a proxy for previous expansion, and rank-frequency, the number of clonotypes at a particular rank, as a proxy for abundance, with the relation of the two estimating the diversity of the system. Previous analyses of circulating antigen-experienced cytotoxic CD8 T-cell repertoires from adults have shown a complex two-component clonotype distribution. Here we show this is also the case for circulating CD8 T cells expressing the BV19 receptor chain from five adult subjects. When the repertoire characteristic of clonotype stability is added to the analysis, an inverse correlation between clonotype rank frequency and stability is observed. Clonotypes making up the second distributional component are stable; indicating that the circulation can be a depot of selected clonotypes. Temporal repertoire dynamics was further examined for influenza-specific T cells from children, middle-aged, and older adults. Taken together, these analyses describe a dynamic process of system development and aging, with increasing distributional complexity, leading to a stable circulating component, followed by loss of both complexity and stability.

Keywords

circulation as depot, computational immunology, human CD8 T cells, repertoire maturation, senescence

Rights and Permissions

Copyright © 2019 Naumova, Yassai, Demos, Reed, Unruh, Haribhai, Williams, Naumov and Gorski. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

DOI of Published Version

10.3389/fimmu.2019.01717

Source

Front Immunol. 2019 Aug 6;10:1717. doi: 10.3389/fimmu.2019.01717. eCollection 2019. Link to article on publisher's site

Journal/Book/Conference Title

Frontiers in immunology

Related Resources

Link to Article in PubMed

PubMed ID

31447830

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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