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

Ramin Sedaghat Herati; Luisa Victoria Silva; Laura A. Vella; Alexander Muselman; Cecile Alanio; Bertram Bengsch; Raj K. Kurupati; Senthil Kannan; Sasikanth Manne; Andrew V. Kossenkov; David H. Canaday; Susan A. Doyle; Hildegund C.J. Ertl; Kenneth E. Schmader; E. John Wherry

Cell Reports Medicine (May 2021)

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

Ramin Sedaghat Herati,
Luisa Victoria Silva,
Laura A. Vella,
Alexander Muselman,
Cecile Alanio,
Bertram Bengsch,
Raj K. Kurupati,
Senthil Kannan,
Sasikanth Manne,
Andrew V. Kossenkov,
David H. Canaday,
Susan A. Doyle,
Hildegund C.J. Ertl,
Kenneth E. Schmader,
E. John Wherry

Affiliations

Ramin Sedaghat Herati: Division of Infectious Diseases and Immunology, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA; Department of Microbiology, New York University School of Medicine, New York, NY, USA; Corresponding author
Luisa Victoria Silva: Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
Laura A. Vella: Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
Alexander Muselman: Department of Immunology, Stanford University, Stanford, CA 94305, USA
Cecile Alanio: Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
Bertram Bengsch: Department of Internal Medicine II, University Medical Center Freiburg, and Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany
Raj K. Kurupati: Wistar Institute, Philadelphia, PA 19104, USA
Senthil Kannan: Wistar Institute, Philadelphia, PA 19104, USA
Sasikanth Manne: Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
Andrew V. Kossenkov: Wistar Institute, Philadelphia, PA 19104, USA
David H. Canaday: Division of Infectious Disease, Case Western Reserve University, Cleveland, OH, USA; Geriatric Research, Education, and Clinical Center, Cleveland VA Medical Center, Cleveland, OH, 44195, USA
Susan A. Doyle: Division of Geriatrics, Department of Medicine, Duke University Medical Center, Durham, NC, USA; Geriatric Research, Education, and Clinical Center, Durham VA Medical Center, Durham, NC 27710, USA
Hildegund C.J. Ertl: Wistar Institute, Philadelphia, PA 19104, USA
Kenneth E. Schmader: Division of Geriatrics, Department of Medicine, Duke University Medical Center, Durham, NC, USA; Geriatric Research, Education, and Clinical Center, Durham VA Medical Center, Durham, NC 27710, USA
E. John Wherry: Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Corresponding author

Journal volume & issue: Vol. 2, no. 5
p. 100262

Abstract

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Summary: 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.

Published in Cell Reports Medicine

ISSN: 2666-3791 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Medicine (General)
Website: https://www.cell.com/cell-reports-medicine

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