Evidence map›Paper›PMID 27335502›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2016

Cytokine-Independent Detection of Antigen-Specific Germinal Center T Follicular Helper Cells in Immunized Nonhuman Primates Using a Live Cell Activation-Induced Marker Technique.

Colin Havenar-Daughton, Samantha M Reiss, Diane G Carnathan, Jennifer E Wu, Kayla Kendric, Alba Torrents de la Peña, Sudhir Pai Kasturi, Jennifer M Dan, Marcella Bothwell, Rogier W Sanders and 3 more

Open access · greenAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed
7.8field-weighted citation impact, top 2% of its field
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

109 citing papers in PubMed, 136 citations in OpenAlex.

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  5. CD4Frontiers in immunology · 2026
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  11. IL-27 effects on HIVFrontiers in virology (Lausanne, Switzerland) · 2025
    Article
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49 more citing papers are in PubMed but not listed here.

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

13 authors at 5 institutions in 2 countries.

Colin Havenar-DaughtonDivision of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla, CA 92037;
Samantha M ReissDivision of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;ORCID 0000-0001-5273-0898
Diane G CarnathanCenter for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla, CA 92037; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322;
Jennifer E WuDivision of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;
Kayla KendricDivision of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;ORCID 0000-0002-6215-9522
Alba Torrents de la PeñaDepartment of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands;
Sudhir Pai KasturiYerkes National Primate Research Center, Emory University, Atlanta, GA 30322; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322;ORCID 0000-0002-6421-2040
Jennifer M DanDivision of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; Division of Infectious Diseases, University of California San Diego, La Jolla, CA 92093;ORCID 0000-0002-1672-0657
Marcella BothwellDepartment of Surgery, University of California San Diego, San Diego, CA 92123; and Pediatric Otolaryngology, Rady Children's Hospital-San Diego, San Diego, CA 92123.ORCID 0000-0001-9771-6221
Rogier W SandersDepartment of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands;
Bali PulendranCenter for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla, CA 92037; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322;
Guido SilvestriCenter for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla, CA 92037; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322;
Shane CrottyDivision of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla, CA 92037; shane@lji.org.ORCID 0000-0002-6484-6262
International AIDS Vaccine Initiative · USLa Jolla Institute for Immunology · USAmsterdam UMC Location University of Amsterdam · NLEmory University · USUniversity of California San Diego · US

Funding

Yerkes National Primate Research Center Role of type-I IFN in regulating COVID-19 induced inflammation and pathogenesisP51OD011132 · OD · EMORY UNIVERSITY · PI Joon Sup Lee · 2012 to 2026
$167.0M
Support Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BAROUCH, DAN H. · 2012 to 2018
$131.5M
YNPRC NHP CLINICAL MEDICINE RESIDENCY PROGRAM - SUPPLEMENTP51RR000165 · NCRR · EMORY UNIVERSITY · PI ALTMAN, JOHN DAVID · 1985 to 2011
$114.0M
Role of Follicular T Helper Cells In Enhancing Humoral Immunity and ProtectionU19AI096187 · NIAID · EMORY UNIVERSITY · PI DERDEYN, CYNTHIA ANN · 2011 to 2015
$26.5M
HOPE Training GrantT32AI007384 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Sara Gianella Weibel, Scott L Letendre · 1990 to 2026
$9.7M
Maximizing germinal centers and somatic hypermutation to HIV Env immunogensR01AI125068 · NIAID · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI CROTTY, SHANE P, IRVINE, DARRELL J · 2016 to 2020
$4.3M
Understanding the Role of Mucosal Antigen Presenting Cells in Regulating Immune ResponseR37AI048638 · NIAID · STANFORD UNIVERSITY · PI PULENDRAN, BALI · 2009 to 2018
$4.0M
FACSAria II Cell SorterS10RR027366 · NCRR · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI CROFT, MICHAEL · 2011 to 2011
$514k
NCRR NIH HHS P51 RR000165NIAID NIH HHS R01 AI125068NIAID NIH HHS R37 AI048638NIAID NIH HHS T32 AI007384NIAID NIH HHS U19 AI096187NIAID NIH HHS UM1 AI100663NIH HHS P51 OD011132
6 · The paper itself

Abstract

A range of current candidate AIDS vaccine regimens are focused on generating protective HIV-neutralizing Ab responses. Many of these efforts rely on the rhesus macaque animal model. Understanding how protective Ab responses develop and how to increase their efficacy are both major knowledge gaps. Germinal centers (GCs) are the engines of Ab affinity maturation. GC T follicular helper (Tfh) CD4 T cells are required for GCs. Studying vaccine-specific GC Tfh cells after protein immunizations has been challenging, as Ag-specific GC Tfh cells are difficult to identify by conventional intracellular cytokine staining. Cytokine production by GC Tfh cells may be intrinsically limited in comparison with other Th effector cells, as the biological role of a GC Tfh cell is to provide help to individual B cells within the GC, rather than secreting large amounts of cytokines bathing a tissue. To test this idea, we developed a cytokine-independent method to identify Ag-specific GC Tfh cells. RNA sequencing was performed using TCR-stimulated GC Tfh cells to identify candidate markers. Validation experiments determined CD25 (IL-2Rα) and OX40 to be highly upregulated activation-induced markers (AIM) on the surface of GC Tfh cells after stimulation. In comparison with intracellular cytokine staining, the AIM assay identified >10-fold more Ag-specific GC Tfh cells in HIV Env protein-immunized macaques (BG505 SOSIP). CD4 T cells in blood were also studied. In summary, AIM demonstrates that Ag-specific GC Tfh cells are intrinsically stingy producers of cytokines, which is likely an essential part of their biological function.

Indexed as

AnimalsBiomarkersCytokinesDisease Models, AnimalFlow CytometryGerminal CenterHIV InfectionsHumansImmunologic TechniquesMacaca mulattaT-Lymphocytes, Helper-InducerBiomarkersCytokines

Identifiers

PMID27335502
PMCPMC4955744
OpenAlexW2474050077

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.