ArticleImmunity2013
Circulating precursor CCR7(lo)PD-1(hi) CXCR5⁺ CD4⁺ T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure.
Article in Immunity, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 395 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
395 citing papers in PubMed, 1 synthesis or guideline pooled it, 645 citations in OpenAlex.
- The soldiers needed to be awakened: Tumor-infiltrating immune cells.Frontiers in genetics · 2022Pooled it
- Efficacy and Safety of Low-Dose Interleukin 2 for Primary Sjögren Syndrome: A Randomized Clinical Trial.JAMA network open · 2022Trial
- Baseline circulating unswitched memory B cells and B-cell related soluble factors are associated with overall survival in patients with clear cell renal cell carcinoma treated with nivolumab within the NIVOREN GETUG-AFU 26 study.Journal for immunotherapy of cancer · 2022Trial
- Efficacy and safety of low-dose interleukin-2 in combination with methotrexate in patients with active rheumatoid arthritis: a randomized, double-blind, placebo-controlled phase 2 trial.Signal transduction and targeted therapy · 2022Trial
- Blood PD-1+TFh and CTLA-4+CD4+ T cells predict remission after CTLA-4Ig treatment in early rheumatoid arthritis.Rheumatology (Oxford, England) · 2022Trial
- Sustained immunotolerance in multiple sclerosis after stem cell transplant.Annals of clinical and translational neurology · 2022Trial
- Protein/AS01Cell reports. Medicine · 2021Trial
- Peripheral CD4+ T cell subsets and antibody response in COVID-19 convalescent individuals.The Journal of clinical investigation · 2020Trial
- Follicular helper T cell profiles predict response to costimulation blockade in type 1 diabetes.Nature immunology · 2020Trial
- IL-21-Deficient T Follicular Helper Cells Support B Cell Responses Through IL-27 in Patients With Chronic Hepatitis B.Frontiers in immunology · 2020Trial
- Targeting T follicular helper cells for lifelong health.Nature reviews. Drug discovery · 2026Review
- Low-dose IL-2 therapy for immune-related adverse events via Tfh/Treg balance modulation: a prospective cohort and murine model study.Cancer immunology, immunotherapy : CII · 2026Article
- Germinal-centre and extrafollicular B cell pathways in systemic lupus erythematosus.Nature reviews. Rheumatology · 2026Review
- Local B cell immunity and durable memory after live-attenuated influenza intranasal vaccination of humans.Science translational medicine · 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
- Circulating TFH2 Cell Expansion and GZMKJournal of asthma and allergy · 2026Article
- Targeted replacement of human γδ TCR in mice enhances antigen-specific B cell immunity.Frontiers in immunology · 2026Article
- Follicular helper-like γδ T cells promote plasma cell differentiation in Behçet's disease.Frontiers in immunology · 2026Article
- The interaction between dendritic cells and T follicular helper cells drives inflammatory bowel disease: a review.Frontiers in immunology · 2026Review
- Effect of CXCR5, PD-1 and ICOS on B-cell responses and relevance to myasthenia gravis.Clinical & translational immunology · 2026Article
335 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 13 institutions in 5 countries.
Funding
Abstract
Follicular B helper T (Tfh) cells support high affinity and long-term antibody responses. Here we found that within circulating CXCR5⁺ CD4⁺ T cells in humans and mice, the CCR7(lo)PD-1(hi) subset has a partial Tfh effector phenotype, whereas CCR7(hi)PD-1(lo) cells have a resting phenotype. The circulating CCR7(lo)PD-1(hi) subset was indicative of active Tfh differentiation in lymphoid organs and correlated with clinical indices in autoimmune diseases. Thus the CCR7(lo)PD-1(hi) subset provides a biomarker to monitor protective antibody responses during infection or vaccination and pathogenic antibody responses in autoimmune diseases. Differentiation of both CCR7(hi)PD-1(lo) and CCR7(lo)PD-1(hi) subsets required ICOS and BCL6, but not SAP, suggesting that circulating CXCR5⁺ helper T cells are primarily generated before germinal centers. Upon antigen reencounter, CCR7(lo)PD-1(hi) CXCR5⁺ precursors rapidly differentiate into mature Tfh cells to promote antibody responses. Therefore, circulating CCR7(lo)PD-1(hi) CXCR5⁺ CD4⁺ T cells are generated during active Tfh differentiation and represent a new mechanism of immunological early memory.
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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.