ArticleProceedings of the National Academy of Sciences of the United States of America2009
Inducible costimulator promotes helper T-cell differentiation through phosphoinositide 3-kinase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers.
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Who cites it
131 citing papers in PubMed, 230 citations in OpenAlex.
- CD4 T cells require ICOS-mediated PI3K signaling to increase T-Bet expression in the setting of anti-CTLA-4 therapy.Cancer immunology research · 2014Trial
- Preoperative CTLA-4 blockade: tolerability and immune monitoring in the setting of a presurgical clinical trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2010Trial
- T cell receptors equipped with ICOS provide T cells with durable anti-tumor response.Molecular cancer · 2026Article
- Inducible Costimulator and Its Ligand Promote Proliferation and Migration of Tumor Cells in Cutaneous T-Cell Lymphoma.International journal of molecular sciences · 2026Article
- Inducible T-Cell Co-Stimulator (ICOS) and ICOS Ligand: Dealing With a Two-Faced Cancer Immunoregulatory System.Cancer medicine · 2026Review
- Integrative Genomic and Transcriptomic Analysis Reveals Targetable Vulnerabilities in Angioimmunoblastic T-Cell Lymphoma.American journal of hematology · 2025Article
- First-in-human phase 1 study of the ICOS agonist feladilimab on patients with advanced solid tumors.Journal for immunotherapy of cancer · 2025Article
- Activated circulating T follicular helper 17 cells positively correlated with anti-HBV humoral immunity in chronic hepatitis B patients.Frontiers in microbiology · 2025Article
- Evolving understanding of autoimmune mechanisms and new therapeutic strategies of autoimmune disorders.Signal transduction and targeted therapy · 2024Review
- Transcriptional regulation of Tfh dynamics and the formation of immunological synapses.Experimental & molecular medicine · 2024Review
- Review
- The differentiation courses of the Tfh cells: a new perspective on autoimmune disease pathogenesis and treatment.Bioscience reports · 2024Review
- Circular RNA CircZNF644 Facilitates Circulating Follicular Helper T Cells Response in Patients with Graves' Disease.Journal of immunology research · 2024Article
- The role of CD4MedComm · 2023Review
- Glucose oxidation-dependent survival of activated B cells provides a putative novel therapeutic target for lupus treatment.iScience · 2023Article
- The role of eIF4F-driven mRNA translation in regulating the tumour microenvironment.Nature reviews. Cancer · 2023Review
- A T follicular helper cell origin for T regulatory type 1 cells.Cellular & molecular immunology · 2023Article
- ICOS costimulation is indispensable for the differentiation of T follicular regulatory cells.Life science alliance · 2023Article
- MiR-29a-3p negatively regulates circulating Tfh memory cells in patients with Graves' disease by targeting ICOS.Immunologic research · 2023Article
- Exosome inspired photo-triggered gelation hydrogel composite on modulating immune pathogenesis for treating rheumatoid arthritis.Journal of nanobiotechnology · 2023Article
71 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The T-cell costimulatory receptors, CD28 and the inducible costimulator (ICOS), are required for the generation of follicular B helper T cells (T(FH)) and germinal center (GC) reaction. A common signal transducer used by CD28 and ICOS is the phosphoinositide 3-kinase (PI3K). Although it is known that CD28-mediated PI3K activation is dispensable for GC reaction, the role of ICOS-driven PI3K signaling has not been defined. We show here that knock-in mice that selectively lost the ability to activate PI3K through ICOS had severe defects in T(FH) generation, GC reaction, antibody class switch, and antibody affinity maturation. In preactivated CD4(+) T cells, ICOS delivered a potent PI3K signal that was critical for the induction of the key T(FH) cytokines, IL-21 and IL-4. Under the same settings, CD28 was unable to activate PI3K but supported a robust secondary expansion of T cells. Thus, our results demonstrate a nonredundant function of ICOS-PI3K pathway in the generation of T(FH) and suggest that CD28 and ICOS play differential roles during a multistep process of T(FH) differentiation.
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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.