ArticleJournal of immunology (Baltimore, Md. : 1950)2016
Immediate Dysfunction of Vaccine-Elicited CD8+ T Cells Primed in the Absence of CD4+ T Cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
42 citing papers in PubMed, 54 citations in OpenAlex.
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- STUB1-mediated ubiquitination regulates Fli-1 stability and CD4⁺T cell activation during inflammation.Molecular medicine (Cambridge, Mass.) · 2026Article
- Stem-like PD-1Journal for immunotherapy of cancer · 2026Article
- Prolonged but finite antigen presentation promotes reversible defects of "helpless" memory CD8Immunity · 2025Article
- Distinct Requirements for CD4European journal of immunology · 2025Article
- Key immune cells and their crosstalk in the tumor microenvironment of bladder cancer: insights for innovative therapies.Exploration of targeted anti-tumor therapy · 2025Review
- Impact of T cell characteristics on CAR-T cell therapy in hematological malignancies.Blood cancer journal · 2024Review
- NitraTh epitope-based neoantigen vaccines for effective tumor immunotherapy.Cancer immunology, immunotherapy : CII · 2024Article
- Lymphoma patients treated with anti-CD20 and chemotherapy display disconnected T and B cell responses to COVID-19 vaccine.Frontiers in immunology · 2024Article
- The expanding Pandora's toolbox of CD8Journal of translational medicine · 2023Review
- The Role of CD4 T Cell Help in CD8 T Cell Differentiation and Function During Chronic Infection and Cancer.Immune network · 2023Review
- The role of CD4MedComm · 2023Review
- Self-assembled nanoparticles based on DNA origami and a nitrated T helper cell epitope as a platform for the development of personalized cancer vaccines.Cancer immunology, immunotherapy : CII · 2023Article
- T cells in health and disease.Signal transduction and targeted therapy · 2023Review
- Lipid A analog CRX-527 conjugated to synthetic peptides enhances vaccination efficacy and tumor control.NPJ vaccines · 2022Article
- An activation to memory differentiation trajectory of tumor-infiltrating lymphocytes informs metastatic melanoma outcomes.Cancer cell · 2022Article
- Low neoantigen expression and poor T-cell priming underlie early immune escape in colorectal cancer.Nature cancer · 2021Article
- Combining spike- and nucleocapsid-based vaccines improves distal control of SARS-CoV-2.Cell reports · 2021Article
- Mechanism of action of PD-1 receptor/ligand targeted cancer immunotherapy.European journal of immunology · 2021Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
CD4(+) T cell help is critical for optimal CD8(+) T cell memory differentiation and maintenance in many experimental systems. In addition, many reports have identified reduced primary CD8(+) T cell responses in the absence of CD4(+) T cell help, which often coincides with reduced Ag or pathogen clearance. In this study, we demonstrate that absence of CD4(+) T cells at the time of adenovirus vector immunization of mice led to immediate impairments in early CD8(+) T cell functionality and differentiation. Unhelped CD8(+) T cells exhibited a reduced effector phenotype, decreased ex vivo cytotoxicity, and decreased capacity to produce cytokines. This dysfunctional state was imprinted within 3 d of immunization. Unhelped CD8(+) T cells expressed elevated levels of inhibitory receptors and exhibited transcriptomic exhaustion and anergy profiles by gene set enrichment analysis. Dysfunctional, impaired effector differentiation also occurred following immunization of CD4(+) T cell-deficient mice with a poxvirus vector. This study demonstrates that following priming with viral vectors, CD4(+) T cell help is required to promote both the expansion and acquisition of effector functions by CD8(+) T cells, which is accomplished by preventing immediate dysfunction.
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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.