ArticleJournal of immunology (Baltimore, Md. : 1950)2017
IL-6 Production by TLR-Activated APC Broadly Enhances Aged Cognate CD4 Helper and B Cell Antibody Responses In Vivo.
Article in Journal of immunology (Baltimore, Md. : 1950), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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.
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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.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Review
- Review
- Immunosenescence: signaling pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Cytotoxic CD4 development requires CD4 effectors to concurrently recognize local antigen and encounter type I IFN-induced IL-15.Cell reports · 2023Article
- CD4 Effector TCR Avidity for Peptide on APC Determines the Level of Memory Generated.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Pathophysiological mechanisms and therapeutic approaches in obstructive sleep apnea syndrome.Signal transduction and targeted therapy · 2023Review
- "Just right" combinations of adjuvants with nanoscale carriers activate aged dendritic cells without overt inflammation.Immunity & ageing : I & A · 2023Article
- CD4 memory has a hierarchical structure created by requirements for infection-derived signals at an effector checkpoint.Frontiers in immunology · 2023Article
- IgDAging cell · 2022Article
- Immunoregulatory Effect of Short-Chain Fatty Acids from Gut Microbiota on Obstructive Sleep Apnea-Associated Hypertension.Nature and science of sleep · 2022Review
- Mechanisms underpinning poor antibody responses to vaccines in ageing.Immunology letters · 2022Review
- Durable CD4 T-Cell Memory Generation Depends on Persistence of High Levels of Infection at an Effector Checkpoint that Determines Multiple Fates.Cold Spring Harbor perspectives in biology · 2021Review
- The impact of immuno-aging on SARS-CoV-2 vaccine development.GeroScience · 2021Review
- "An Intrinsic Program Determines Key Age-Associated Changes in Adaptive Immunity that Limit Response to Non-Pathogens."Frontiers in aging · 2021Article
- Influenza Vaccine-Induced CD4 Effectors Require Antigen Recognition at an Effector Checkpoint to Generate CD4 Lung Memory and Antibody Production.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Influenza vaccination strategies targeting the hemagglutinin stem region.Immunological reviews · 2020Review
- Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccination.eLife · 2020Article
- Understanding the Heterogeneous Population of Age-Associated B Cells and Their Contributions to Autoimmunity and Immune Response to Pathogens.Critical reviews in immunology · 2020Article
- RNA-Seq Analysis of Colorectal Tumor-Infiltrating Myeloid-Derived Suppressor Cell Subsets Revealed Gene Signatures of Poor Prognosis.Frontiers in oncology · 2020Article
- Inhibition of fatty acid metabolism by etomoxir or TOFA suppresses murine dendritic cell activation without affecting viability.Immunopharmacology and immunotoxicology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Naive CD4 T cell responses, especially their ability to help B cell responses, become compromised with aging. We find that using APC pretreated ex vivo with TLR agonists, polyinosinic-polycytidylic acid and CpG, to prime naive CD4 T cells in vivo, restores their ability to expand and become germinal center T follicular helpers and enhances B cell IgG Ab production. Enhanced helper responses are dependent on IL-6 production by the activated APC. Aged naive CD4 T cells respond suboptimally to IL-6 compared with young cells, such that higher doses are required to induce comparable signaling. Preactivating APC overcomes this deficiency. Responses of young CD4 T cells are also enhanced by preactivating APC with similar effects but with only partial IL-6 dependency. Strikingly, introducing just the activated APC into aged mice significantly enhances otherwise compromised Ab production to inactivated influenza vaccine. These findings reveal a central role for the production of IL-6 by APC during initial cognate interactions in the generation of effective CD4 T cell help, which becomes greater with age. Without APC activation, aging CD4 T cell responses shift toward IL-6-independent Th1 and CD4 cytotoxic Th cell responses. Thus, strategies that specifically activate and provide Ag to APC could potentially enhance Ab-mediated protection in vaccine responses.
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Registered trials
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.