ArticleThe Journal of experimental medicine2015
ICOS maintains the T follicular helper cell phenotype by down-regulating Krüppel-like factor 2.
Article in The Journal of experimental medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 184 papers, 2 of them syntheses 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
184 citing papers in PubMed, 2 syntheses or guidelines pooled it, 286 citations in OpenAlex.
- Pediatric CD4+ Small Medium Sized Pleomorphic T-cell Lymphoproliferative Disorder: A Unique Indolent Lymphoproliferative Lesion With Consistent Reproducible Clinical and Phenotypic Features.The American Journal of dermatopathology · 2025Pooled it
- The soldiers needed to be awakened: Tumor-infiltrating immune cells.Frontiers in genetics · 2022Pooled it
- Follicular helper T cell profiles predict response to costimulation blockade in type 1 diabetes.Nature immunology · 2020Trial
- Abatacept Targets T Follicular Helper and Regulatory T Cells, Disrupting Molecular Pathways That Regulate Their Proliferation and Maintenance.Journal of immunology (Baltimore, Md. : 1950) · 2019Trial
- Article
- Ets1 represses Blimp1 to promote germinal center T follicular helper cell differentiation during viral infection.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- IL-1β and IL-6 synergistically drive murine TFH cell differentiation and maintenance in vitro.Immunology and cell biology · 2026Article
- Functions and features of circulating memory T cells.Immunity · 2026Review
- Single Cell Analysis Reveals Dynamic Changes of Distinct Cell Populations in Human Nickel Allergy.Allergy · 2026Article
- Dnmt3a-dependent de novo DNA methylation enforces lineage commitment and preserves functionality of memory Th1 and Tfh cells.Cell reports · 2026Article
- Divergent phenotypic and functional roles of human T follicular helper cells from infancy to adulthood.bioRxiv : the preprint server for biology · 2026Article
- Pre-Existing Th1 Immunity Outperforms Age in Predicting Antibody Responses to SARS-CoV-2 Inactivated Vaccines.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Inducible T-Cell Co-Stimulator (ICOS) and ICOS Ligand: Dealing With a Two-Faced Cancer Immunoregulatory System.Cancer medicine · 2026Review
- Multimodal analysis definesbioRxiv : the preprint server for biology · 2025Article
- The STING/type I interferon axis drives the interplay between marginal zone B cells and T follicular helper cells in Sjögren's disease.Cellular & molecular immunology · 2025Article
- Lymph nodes fuel KLF2-dependent effector CD8Nature immunology · 2025Article
- Second signals for cancer immunotherapy.Journal for immunotherapy of cancer · 2025Review
- The costimulatory molecule ICOS limits memory-like properties and function of exhausted PD-1Immunity · 2025Article
- Mitochondrial DNA oxidation propagates autoimmunity by enabling plasmacytoid dendritic cells to induce TNature immunology · 2025Article
- Mitigation of Ferroptosis in Diabetic Kidney Disease Through Mesenchymal Stem Cell Intervention via the Smad2/3/METTL3/S1PR1 Axis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
124 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The co-stimulators ICOS (inducible T cell co-stimulator) and CD28 are both important for T follicular helper (TFH) cells, yet their individual contributions are unclear. Here, we show that each molecule plays an exclusive role at different stages of TFH cell development. While CD28 regulated early expression of the master transcription factor Bcl-6, ICOS co-stimulation was essential to maintain the phenotype by regulating the novel TFH transcription factor Klf2 via Foxo1. Klf2 directly binds to Cxcr5, Ccr7, Psgl-1, and S1pr1, and low levels of Klf2 were essential to maintain this typical TFH homing receptor pattern. Blocking ICOS resulted in relocation of fully developed TFH cells back to the T cell zone and reversion of their phenotype to non-TFH effector cells, which ultimately resulted in breakdown of the germinal center response. Our study describes for the first time the exclusive role of ICOS and its downstream signaling in the maintenance of TFH cells by controlling their anatomical localization in the B cell follicle.
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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.