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

doi:10.1016/j.xcrm.2021.100262

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

Cell Rep Med. 2021 May 7;2(5):100262. doi: 10.1016/j.xcrm.2021.100262. eCollection 2021 May 18.

Authors

Ramin Sedaghat Herati^{1

2}, Luisa Victoria Silva³, Laura A Vella^{3

4}, Alexander Muselman⁵, Cecile Alanio^{3

6}, Bertram Bengsch⁷, Raj K Kurupati⁸, Senthil Kannan⁸, Sasikanth Manne^{3

6}, Andrew V Kossenkov⁸, David H Canaday^{9

10}, Susan A Doyle^{11

12}, Hildegund C J Ertl⁸, Kenneth E Schmader^{11

12}, E John Wherry^{3

6}

Affiliations

¹ Division of Infectious Diseases and Immunology, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA.
² Department of Microbiology, New York University School of Medicine, New York, NY, USA.
³ Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
⁴ Department of Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
⁵ Department of Immunology, Stanford University, Stanford, CA 94305, USA.
⁶ Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
⁷ Department of Internal Medicine II, University Medical Center Freiburg, and Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.
⁸ Wistar Institute, Philadelphia, PA 19104, USA.
⁹ Division of Infectious Disease, Case Western Reserve University, Cleveland, OH, USA.
¹⁰ Geriatric Research, Education, and Clinical Center, Cleveland VA Medical Center, Cleveland, OH, 44195, USA.
¹¹ Division of Geriatrics, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
¹² Geriatric Research, Education, and Clinical Center, Durham VA Medical Center, Durham, NC 27710, USA.

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.

Keywords: CD4; NF-kB; T follicular helper; aging; cellular biosensors; influenza; network analysis; vaccine.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Age Factors*
B-Lymphocytes / immunology*
Humans
Immunity, Humoral / immunology
Inducible T-Cell Co-Stimulator Protein / immunology
Inducible T-Cell Co-Stimulator Protein / metabolism*
Inflammation / immunology
Inflammation / metabolism*
Lymphocyte Activation / immunology
Lymphocyte Count / methods
T-Lymphocytes, Helper-Inducer / immunology*
Vaccination / methods
Vaccines / metabolism

Substances

ICOS protein, human
Inducible T-Cell Co-Stimulator Protein
Vaccines

Abstract

Publication types

MeSH terms

Substances

Grants and funding