ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Vaccination Produces CD4 T Cells with a Novel CD154-CD40-Dependent Cytolytic Mechanism.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Combined skin and muscle vaccination differentially impact the quality of effector T cell functions: the CUTHIVAC-001 randomized trial.Scientific reports · 2017Trial
- The Role of CD4 T Cell Repertoire and Immune Memory Mechanisms in Vaccination and Infection Immunity.Immunological reviews · 2026Review
- Heterologous vaccination with a next-generation vaccinia virus and Ad26 induces Ebola-specific immunity in macaques.NPJ vaccines · 2026Article
- Recent Evidence of the Role of CD4JMA journal · 2025Review
- Immunogenicity and protection against Mycobacterium avium with a heterologous RNA prime and protein boost vaccine regimen.Tuberculosis (Edinburgh, Scotland) · 2023Article
- Mapping and role of T cell response in SARS-CoV-2-infected mice.The Journal of experimental medicine · 2021Article
- Prophylactic efficacy against Mycobacterium tuberculosis using ID93 and lipid-based adjuvant formulations in the mouse model.PloS one · 2021Article
- Concepts for agonistic targeting of CD40 in immuno-oncology.Human vaccines & immunotherapeutics · 2020Review
- Many Th Cell Subsets Have Fas Ligand-Dependent Cytotoxic Potential.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- The role of toll-like receptor 4 in tumor microenvironment.Oncotarget · 2017Review
- Fighting Viral Infections and Virus-Driven Tumors with Cytotoxic CD4Frontiers in immunology · 2017Review
- MHC class II tetramer analyses in AE37-vaccinated prostate cancer patients reveal vaccine-specific polyfunctional and long-lasting CD4(+) T-cells.Oncoimmunology · 2016Article
- The Differentiation and Protective Function of Cytolytic CD4 T Cells in Influenza Infection.Frontiers in immunology · 2016Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The discovery of new vaccines against infectious diseases and cancer requires the development of novel adjuvants with well-defined activities. The TLR4 agonist adjuvant GLA-SE elicits robust Th1 responses to a variety of vaccine Ags and is in clinical development for both infectious diseases and cancer. We demonstrate that immunization with a recombinant protein Ag and GLA-SE also induces granzyme A expression in CD4 T cells and produces cytolytic cells that can be detected in vivo. Surprisingly, these in vivo CTLs were CD4 T cells, not CD8 T cells, and this cytolytic activity was not dependent on granzyme A/B or perforin. Unlike previously reported CD4 CTLs, the transcription factors Tbet and Eomes were not necessary for their development. CTL activity was also independent of the Fas ligand-Fas, TRAIL-DR5, and canonical death pathways, indicating a novel mechanism of CTL activity. Rather, the in vivo CD4 CTL activity induced by vaccination required T cell expression of CD154 (CD40L) and target cell expression of CD40. Thus, vaccination with a TLR4 agonist adjuvant induces CD4 CTLs, which kill through a previously unknown CD154-dependent mechanism.
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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.