ArticleImmunity2011
ICOS receptor instructs T follicular helper cell versus effector cell differentiation via induction of the transcriptional repressor Bcl6.
Article in Immunity, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 600 papers, 1 of them a synthesis that pooled it.
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Who cites it
600 citing papers in PubMed, 1 synthesis or guideline pooled it, 919 citations in OpenAlex.
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- Protein/AS01Cell reports. Medicine · 2021Trial
- H2-O deficiency in B cells or dendritic cells drives retrovirus-neutralizing antibody responses.Journal of virology · 2026Article
- Surface display of co-stimulatory ligand B7H2 on engineered bacteria enhances tumor immunotherapy.Cell reports. Medicine · 2026Article
- A favorable follicular helper CD4+ T cell programming characterizes neutralization activity in chronic HIV infection.The Journal of clinical investigation · 2026Article
- T cell lymphomas: cancers of aberrant immune synapse signalling.Nature reviews. Immunology · 2026Review
- The Role of CD4 T Cell Repertoire and Immune Memory Mechanisms in Vaccination and Infection Immunity.Immunological reviews · 2026Review
- TGF-β and IL-2 differentially shape T follicular regulatory cell differentiation and stability in vitro.Cellular & molecular immunology · 2026Article
- Defective inducible T cell costimulator signalling drives neuropilin-1Experimental & molecular medicine · 2026Article
- Ets1 represses Blimp1 to promote germinal center T follicular helper cell differentiation during viral infection.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- B Cell Subsets and Atherosclerosis: Updates and Emerging Concepts.Immunological reviews · 2026Review
- Dnmt3a-dependent de novo DNA methylation enforces lineage commitment and preserves functionality of memory Th1 and Tfh cells.Cell reports · 2026Article
- Impaired T Follicular Regulatory Cell Function and Enhanced T Follicular Helper Cell Activity in Experimental Autoimmune Encephalomyelitis: Mechanistic Insights into CNS Autoimmunity.International journal of molecular sciences · 2026Article
- Proposition for a New Classification of Hypersensitivity Reactions - an Expanded Nomenclature.Clinical reviews in allergy & immunology · 2026Review
- Divergent phenotypic and functional roles of human T follicular helper cells from infancy to adulthood.bioRxiv : the preprint server for biology · 2026Article
- Inducible T-Cell Co-Stimulator (ICOS) and ICOS Ligand: Dealing With a Two-Faced Cancer Immunoregulatory System.Cancer medicine · 2026Review
- Functional profiling of porcine precision-cut lymph node slices as anFrontiers in immunology · 2026Article
- Sex in Immune Cells and Parasitic Diseases - A Complex Relationship.Immunological reviews · 2026Review
540 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The nature of follicular helper CD4(+) T (Tfh) cell differentiation remains controversial, including the minimal signals required for Tfh cell differentiation and the time at which Tfh cell differentiation occurs. Here we determine that Tfh cell development initiates immediately during dendritic cell (DC) priming in vivo. We demonstrate that inducible costimulator (ICOS) provides a critical early signal to induce the transcription factor Bcl6, and Bcl6 then induces CXCR5, the canonical feature of Tfh cells. Strikingly, a bifurcation between Tfh and effector Th cells was measurable by the second cell division of CD4(+) T cells, at day 2 after an acute viral infection: IL2Rα(int) cells expressed Bcl6 and CXCR5 (Tfh cell program), whereas IL2Rα(hi) cells exhibited strong Blimp1 expression that repressed Bcl6 (effector Th cell program). Virtually complete polarization between Bcl6(+) Tfh cells and Blimp1(+) effector Th cell populations developed by 72 hr, even without B cells. Tfh cells were subsequently lost in the absence of B cells, demonstrating a B cell requirement for maintenance of Bcl6 and Tfh cell commitment via sequential ICOS signals.
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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.