期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：34
DOI：10.1073/pnas.2201541119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
While making virus-specific immune responses to SARS-CoV-2, residual B and T cell diversity are key to making responses to concurrent co-infections and/or cancers. We applied an antigen receptor–sequencing technology and provide a comprehensive description of the global immune repertoire in hospitalized and nonhospitalized individuals infected with SARS-CoV-2. Although B cell diversity predictably narrowed, significant narrowing of αβ and γδ T cell diversity was unexpectedly observed only in those aged over 50, which is a major inflexion point for COVID-19–associated mortality. Such a discrepancy in how older persons mount T cell responses to a new virus may be considered a risk factor for the elderly, particularly vis-à-vis new virus variants against which T cell immunity may be particularly important.
Whereas pathogen-specific T and B cells are a primary focus of interest during infectious disease, we have used COVID-19 to ask whether their emergence comes at a cost of broader B cell and T cell repertoire disruption. We applied a genomic DNA-based approach to concurrently study the immunoglobulin-heavy (IGH) and T cell receptor (TCR) β and δ chain loci of 95 individuals. Our approach detected anticipated repertoire focusing for the IGH repertoire, including expansions of clusters of related sequences temporally aligned with SARS-CoV-2–specific seroconversion, and enrichment of some shared SARS-CoV-2–associated sequences. No significant age-related or disease severity–related deficiencies were noted for the IGH repertoire. By contrast, whereas focusing occurred at the TCRβ and TCRδ loci, including some TCRβ sequence–sharing, disruptive repertoire narrowing was almost entirely limited to many patients aged older than 50 y. By temporarily reducing T cell diversity and by risking expansions of nonbeneficial T cells, these traits may constitute an age-related risk factor for COVID-19, including a vulnerability to new variants for which T cells may provide key protection.
