Evidence map›Paper›PMID 41727083›Full record

ArticlebioRxiv : the preprint server for biology2026

Divergent phenotypic and functional roles of human T follicular helper cells from infancy to adulthood.

Suhas Sureshchandra, Jenna M Kastenschmidt, Erika M Joloya, Zachary W Wagoner, Arjun K Nair, Samuel Kim, Natalie Zane, Gargee Bhattacharya, Alyssa M Monterroso, Evien Cheng and 15 more

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In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors.

Suhas SureshchandraDepartment of Physiology & Biophysics, Institute for Immunology, Center for Virus Research, Adeline Yen Mah Vaccine Center, and Cancer Research Institute, University of California Irvine, Irvine, Irvine, USA.ORCID 0000-0002-4141-8564
Jenna M KastenschmidtDepartment of Physiology & Biophysics, Institute for Immunology, Center for Virus Research, Adeline Yen Mah Vaccine Center, and Cancer Research Institute, University of California Irvine, Irvine, Irvine, USA.ORCID 0000-0002-0067-5142
Erika M JoloyaDepartment of Physiology & Biophysics, Institute for Immunology, Center for Virus Research, Adeline Yen Mah Vaccine Center, and Cancer Research Institute, University of California Irvine, Irvine, Irvine, USA.ORCID 0000-0002-4974-1657
Zachary W WagonerDepartment of Physiology & Biophysics, Institute for Immunology, Center for Virus Research, Adeline Yen Mah Vaccine Center, and Cancer Research Institute, University of California Irvine, Irvine, Irvine, USA.ORCID 0000-0002-0354-5407
Arjun K NairDepartment of Physiology & Biophysics, Institute for Immunology, Center for Virus Research, Adeline Yen Mah Vaccine Center, and Cancer Research Institute, University of California Irvine, Irvine, Irvine, USA.
Samuel KimDepartment of Physiology & Biophysics, Institute for Immunology, Center for Virus Research, Adeline Yen Mah Vaccine Center, and Cancer Research Institute, University of California Irvine, Irvine, Irvine, USA.
Natalie ZaneDepartment of Physiology & Biophysics, Institute for Immunology, Center for Virus Research, Adeline Yen Mah Vaccine Center, and Cancer Research Institute, University of California Irvine, Irvine, Irvine, USA.ORCID 0009-0009-7385-4262
Gargee BhattacharyaDepartment of Physiology & Biophysics, Institute for Immunology, Center for Virus Research, Adeline Yen Mah Vaccine Center, and Cancer Research Institute, University of California Irvine, Irvine, Irvine, USA.ORCID 0000-0002-6129-3965
Alyssa M MonterrosoDepartment of Physiology & Biophysics, Institute for Immunology, Center for Virus Research, Adeline Yen Mah Vaccine Center, and Cancer Research Institute, University of California Irvine, Irvine, Irvine, USA.ORCID 0000-0001-6137-0169
Evien ChengDepartment of Physiology & Biophysics, Institute for Immunology, Center for Virus Research, Adeline Yen Mah Vaccine Center, and Cancer Research Institute, University of California Irvine, Irvine, Irvine, USA.ORCID 0009-0008-4379-0790
Andrew M SornDepartment of Physiology & Biophysics, Institute for Immunology, Center for Virus Research, Adeline Yen Mah Vaccine Center, and Cancer Research Institute, University of California Irvine, Irvine, Irvine, USA.
Mahina Tabassum MitulDepartment of Physiology & Biophysics, Institute for Immunology, Center for Virus Research, Adeline Yen Mah Vaccine Center, and Cancer Research Institute, University of California Irvine, Irvine, Irvine, USA.ORCID 0000-0002-5344-6810
Haven BearesDepartment of Physiology & Biophysics, Institute for Immunology, Center for Virus Research, Adeline Yen Mah Vaccine Center, and Cancer Research Institute, University of California Irvine, Irvine, Irvine, USA.ORCID 0009-0002-7645-6648
Germaine MendezDepartment of Physiology & Biophysics, Institute for Immunology, Center for Virus Research, Adeline Yen Mah Vaccine Center, and Cancer Research Institute, University of California Irvine, Irvine, Irvine, USA.
Timothy B YatesDepartment of Physiology & Biophysics, Institute for Immunology, Center for Virus Research, Adeline Yen Mah Vaccine Center, and Cancer Research Institute, University of California Irvine, Irvine, Irvine, USA.ORCID 0009-0004-7943-9493
Fan ZhouInfluenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway.
Allyssa DaughertyDepartment of Neurology Bursky Center for Human Immunology and Immunotherapy Programs; Hope Center for Neurological Disorders; Center for Brain Immunology and Glia (BIG), Siteman Cancer Center, Washington University School of Medicine, St. Louis, USA.
Chandrani ThakurDepartment of Neurology Bursky Center for Human Immunology and Immunotherapy Programs; Hope Center for Neurological Disorders; Center for Brain Immunology and Glia (BIG), Siteman Cancer Center, Washington University School of Medicine, St. Louis, USA.
Karl A BrokstadInfluenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway.ORCID 0000-0003-0593-2731
Douglas TraskDepartment of Otolaryngology and Head & Neck Surgery, University of California, Irvine, USA.ORCID 0000-0003-0550-442X
Gurpreet AhujaDepartment of Otolaryngology, Children's Hospital of Orange County, Orange, USA.
Qiu ZhongDepartment of Otolaryngology, Children's Hospital of Orange County, Orange, USA.
Naresha SaligramaDepartment of Neurology Bursky Center for Human Immunology and Immunotherapy Programs; Hope Center for Neurological Disorders; Center for Brain Immunology and Glia (BIG), Siteman Cancer Center, Washington University School of Medicine, St. Louis, USA.ORCID 0000-0003-2526-7150
Rebecca J CoxInfluenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway.
Lisa E WagarDepartment of Physiology & Biophysics, Institute for Immunology, Center for Virus Research, Adeline Yen Mah Vaccine Center, and Cancer Research Institute, University of California Irvine, Irvine, Irvine, USA.ORCID 0000-0001-5980-3586

Funding

Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI TIMOTHY J. EBERLEIN · 2001 to 2026
$128.0M
Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Melanie Funes · 1994 to 2026
$57.9M
Shared Resource Core: Single Cell AnalysisU54CA217378 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI LANDER, ARTHUR D · 2018 to 2022
$9.7M
UCI P30 Skin Center Systems Biology CoreP30AR075047 · NIAMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI LANDER, ARTHUR D · 2019 to 2025
$5.1M
Investigating protective adaptive immune responses to influenza antigens using human tonsil organoidsR01AI173023 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI Lisa Wagar · 2023 to 2026
$2.5M
PacBio RS Single Molecule, Real-Time (SMRT) DNA SequencerS10OD010794 · OD · UNIVERSITY OF CALIFORNIA-IRVINE · PI SANDMEYER, SUZANNE · 2012 to 2012
$600k
High-Throughput DNA SequencerS10OD021718 · OD · UNIVERSITY OF CALIFORNIA-IRVINE · PI SANDMEYER, SUZANNE · 2016 to 2016
$600k
High Throughput DNA SequencerS10RR025496 · NCRR · UNIVERSITY OF CALIFORNIA-IRVINE · PI SANDMEYER, SUZANNE · 2009 to 2009
$500k
Targeting T follicular helper cells for rejuvenating the aging germinal centerK99AG090739 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI Suhas Sureshchandra · 2025 to 2026
$254k
NCI NIH HHS P30 CA062203NCI NIH HHS P30 CA091842NCI NIH HHS U54 CA217378NCRR NIH HHS S10 RR025496NIAID NIH HHS R01 AI173023NIAMS NIH HHS P30 AR075047NIA NIH HHS K99 AG090739NIH HHS S10 OD010794NIH HHS S10 OD021718Wellcome Trust
6 · The paper itself

Abstract

Antibody responses to T-dependent antigens are suboptimal in young children, yet the evolution of T follicular helper cell (Tfh) function across the human lifespan remains poorly defined. Using human tonsils, a physiologically relevant and abundant source of Tfh, we investigated age-associated differences in their repertoire and functional programs. Pediatric tonsils were enriched for cytokine-expressing Tfh subsets with increased clonal diversity and phenotypic plasticity. However, in response to influenza antigens, they exhibited reduced Th1 polarization, diminished IL-21 production, and limited B cell help. Across ages, high neutralizing flu antibody responses were associated with robust Tfh1 activation, which was ICOS dependent in adults but not in children. Interestingly, Tfh depletion strategies revealed enhanced Tfh differentiation from distinct precursors in pediatric donors, yet antibody responses during early life were less reliant on Tfh help. Together, these findings define developmentally programmed differences in Tfh differentiation and function with implications for pediatric vaccine design.

Identifiers

PMID41727083
PMCPMC12919020

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.