ArticlePloS one2014
Inflammation enhances IL-2 driven differentiation of cytolytic CD4 T cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
- Identifying Negative Biomarkers of CD4 Cytotoxic T Lymphocytes via Granzyme B Exclusion Analysis.European journal of immunology · 2026Article
- Cytotoxic Programming of CD4+ T Cells Is Regulated by Opposing Actions of the Related Transcription Factors Eos and Aiolos.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- CTLs heterogeneity and plasticity: implications for cancer immunotherapy.Molecular cancer · 2024Review
- T cells in health and disease.Signal transduction and targeted therapy · 2023Review
- Expression analysis of IL-2, TBX21 and SOCS1 in peripheral blood cells of celiac disease patients reveals the diagnostic potential of IL-2.Molecular biology reports · 2023Article
- Aiolos represses CD4Nature communications · 2023Article
- Low perforin expression in CD8+ T lymphocytes during the acute phase of severe SARS-CoV-2 infection predicts long COVID.Frontiers in immunology · 2022Article
- Article
- The Era of Cytotoxic CD4 T Cells.Frontiers in immunology · 2022Review
- CD127+ CD94+ innate lymphoid cells expressing granulysin and perforin are expanded in patients with Crohn's disease.Nature communications · 2021Article
- Identification of human cytotoxic ILC3s.European journal of immunology · 2021Article
- Immunity to Influenza Infection in Humans.Cold Spring Harbor perspectives in medicine · 2021Review
- Mucosal IL-4R antagonist HIV vaccination with SOSIP-gp140 booster can induce high-quality cytotoxic CD4Scientific reports · 2020Article
- Distinct and complementary roles of CD4 T cells in protective immunity to influenza virus.Current opinion in immunology · 2018Review
- CD4 T cells in protection from influenza virus: Viral antigen specificity and functional potential.Immunological reviews · 2018Review
- An Immunotherapeutic CD137 Agonist Releases Eomesodermin from ThPOK Repression in CD4 T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Interleukins 12 and 15 induce cytotoxicity and early NK-cell differentiation in type 3 innate lymphoid cells.Blood advances · 2017Article
- NKG2C/E Marks the Unique Cytotoxic CD4 T Cell Subset, ThCTL, Generated by Influenza Infection.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Cytotoxic CD4 T Cells-Friend or Foe during Viral Infection?Frontiers in immunology · 2017Review
- Fighting Viral Infections and Virus-Driven Tumors with Cytotoxic CD4Frontiers in immunology · 2017Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Cytolytic CD4 T cells (CD4 CTL) have been identified in vivo in response to viral infections; however, the factors necessary for driving the cytolytic phenotype have not been fully elucidated. Our previously published work suggests IL-2 may be the master regulator of perforin-mediated cytotoxicity in CD4 effectors. To further dissect the role of IL-2 in CD4 CTL generation, T cell receptor transgenic mice deficient in the ability to produce IL-2 or the high affinity IL-2 receptor (IL-2Rα, CD25) were used. Increasing concentrations of IL-2 were necessary to drive perforin (Prf) expression and maximal cytotoxicity. Granzyme B (GrB) expression and killing correlated with STAT5 activation and CD25 expression in vitro, suggesting that signaling through the high affinity IL-2R is critical for full cytotoxicity. IL-2 signaling was also necessary in vivo for inducing the Th1 phenotype and IFN-γ expression in CD4 T cells during influenza A (IAV) infection. In addition, GrB expression, as measured by mean fluorescent intensity, was decreased in CD25 deficient cells; however, the frequency of CD4 cells expressing GrB was unchanged. Similarly, analysis of cytolytic markers such as CD107a/b and Eomesodermin indicate high IL-2Rα expression is not necessary to drive the CD4 CTL phenotype during IAV infection. Thus, inflammatory signals induced by viral infection may overcome the need for strong IL-2 signals in driving cytotoxicity in CD4 cells.
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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.