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Vaccine-induced ICOS+CD38+ circulating Tfh are sensitive biosensors of age-related changes in inflammatory pathways.


ABSTRACT: Humoral immune responses are dysregulated with aging, but the cellular and molecular pathways involved remain incompletely understood. In particular, little is known about the effects of aging on T follicular helper (Tfh) CD4 cells, the key cells that provide help to B cells for effective humoral immunity. We performed transcriptional profiling and cellular analysis on circulating Tfh before and after influenza vaccination in young and elderly adults. First, whole-blood transcriptional profiling shows that ICOS+CD38+ cTfh following vaccination preferentially enriches in gene sets associated with youth versus aging compared to other circulating T cell types. Second, vaccine-induced ICOS+CD38+ cTfh from the elderly had increased the expression of genes associated with inflammation, including tumor necrosis factor-nuclear factor κB (TNF-NF-κB) pathway activation. Finally, vaccine-induced ICOS+CD38+ cTfh display strong enrichment for signatures of underlying age-associated biological changes. These data highlight the ability to use vaccine-induced cTfh as cellular "biosensors" of underlying inflammatory and/or overall immune health.

SUBMITTER: Herati RS 

PROVIDER: S-EPMC8149371 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Vaccine-induced ICOS<sup>+</sup>CD38<sup>+</sup> circulating Tfh are sensitive biosensors of age-related changes in inflammatory pathways.

Herati Ramin Sedaghat RS   Silva Luisa Victoria LV   Vella Laura A LA   Muselman Alexander A   Alanio Cecile C   Bengsch Bertram B   Kurupati Raj K RK   Kannan Senthil S   Manne Sasikanth S   Kossenkov Andrew V AV   Canaday David H DH   Doyle Susan A SA   Ertl Hildegund C J HCJ   Schmader Kenneth E KE   Wherry E John EJ  

Cell reports. Medicine 20210507 5


Humoral immune responses are dysregulated with aging, but the cellular and molecular pathways involved remain incompletely understood. In particular, little is known about the effects of aging on T follicular helper (Tfh) CD4 cells, the key cells that provide help to B cells for effective humoral immunity. We performed transcriptional profiling and cellular analysis on circulating Tfh before and after influenza vaccination in young and elderly adults. First, whole-blood transcriptional profiling  ...[more]

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