ArticlePLoS biology2019
Dysfunctional peripheral T follicular helper cells dominate in people with impaired influenza vaccine responses: Results from the FLORAH study.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 43 citations in OpenAlex.
- High-dose influenza vaccine augments serological and cellular immunity of older people with HIV.JCI insight · 2026Article
- Altered Cytokine-Induced STAT3 and STAT5 Activation of Peripheral T Follicular Helper Cells Contributes to Vaccine-Non-Responsiveness in Aging and HIV.Aging cell · 2026Article
- Phenotypic, functional and metabolic features of B cells from a small cohort of breast cancer patients.Frontiers in oncology · 2026Article
- Immune Alterations and Viral Reservoir Atlas in SIV-Infected Chinese Rhesus Macaques.Infectious disease reports · 2025Review
- Human genetics of responses to vaccines.Clinical and experimental immunology · 2025Review
- Bioinformatics approach reveals the critical role of inflammation-related genes in age-related hearing loss.Scientific reports · 2025Article
- Chronic opioid use is associated with higher antibody response to influenza vaccination in people living with HIV.Frontiers in immunology · 2025Article
- Accelerated CD8iScience · 2024Article
- Article
- Destabilisation of T cell-dependent humoral immunity in sepsis.Clinical science (London, England : 1979) · 2024Review
- ATP-P2X7R pathway activation limits the Tfh cell compartment during pediatric RSV infection.Frontiers in immunology · 2024Article
- IL-21-IgFc immunotherapy alters transcriptional landscape of lymph node cells leading to enhanced flu vaccine response in aging and SIV infection.Aging cell · 2023Article
- An Overview of Miami CDEIPI and a Showcase of Team Science and Cutting-Edge Research Driven by Students.Journal of acquired immune deficiency syndromes (1999) · 2023Article
- Living with HIV and Getting Vaccinated: A Narrative Review.Vaccines · 2023Review
- Opioids exacerbate inflammation in people with well-controlled HIV.Frontiers in immunology · 2023Article
- Distinct immunological and molecular signatures underpinning influenza vaccine responsiveness in the elderly.Nature communications · 2022Article
- Perinatally Human Immunodeficiency Virus-Infected Adolescents and Young Adults Demonstrate Distinct BNT162b2 Messenger RNA Coronavirus Disease 2019 Vaccine Immunogenicity.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Article
- Antigen-Specific CD4Frontiers in immunology · 2022Article
- Abnormal Shift in B Memory Cell Profile Is Associated With the Expansion of Circulating T Follicular Helper CellsFrontiers in immunology · 2022Article
- IL-21 enhances influenza vaccine responses in aged macaques with suppressed SIV infection.JCI insight · 2021Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Antigen-primed cluster of differentiation (CD) 4+ T follicular helper (Tfh) cells interact with B cells in the germinal centers (GCs) of lymph nodes to generate vaccine-induced antibody (Ab) responses. In the circulation, peripheral Tfh (pTfh) cells, a subset of memory CD4 T cells, serve as surrogates for GC Tfh because of several functional and phenotypic similarities between them. We investigated features of H1N1 influenza antigen-specific pTfh (Ag.pTfh) in virologically controlled HIV+ volunteers on antiretroviral therapy (ART) and healthy control (HC) participants selected from a seasonal influenza vaccine responsiveness study. Selection of the participants was made based on age, defined as young (18-40 y) and old (>60 y) and on their classification as a vaccine responder (VR) or vaccine nonresponder (VNR). VRs demonstrated expansion of CD40L+ and CD69+ Ag.pTfh, with induction of intracellular interleukin 21 (IL-21) and inducible costimulator (ICOS) post vaccination; these responses were strongest in young HC VRs and were less prominent in HIV+ individuals of all ages. Ag.pTfh in VNRs exhibited dramatically different characteristics from VRs, displaying an altered phenotype and a cytokine profile dominated by cytokines IL-2, tumor necrosis factor alpha (TNF-α), or IL-17 but lacking in IL-21. In coculture experiments, sorted pTfh did not support the B cell IgG production in VNRs and were predominantly an inflammatory T helper 1 (Th1)/T helper 17 (Th17) phenotype with lower ICOS and higher programmed cell death protein 1 (PD1) expression. Induction of IL-21 and ICOS on Ag.pTfh cells are negatively affected by both aging and HIV infection. Our findings demonstrate that dysfunctional Ag.pTfh cells with an altered IL-21/IL-2 axis contribute to inadequate vaccine responses. Approaches for targeting inflammation or expanding functional Tfh may improve vaccine responses in healthy aging and those aging with HIV infection.
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