ArticlePLoS pathogens2016
Cytomegalovirus Infection Leads to Development of High Frequencies of Cytotoxic Virus-Specific CD4+ T Cells Targeted to Vascular Endothelium.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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Who cites it
102 citing papers in PubMed, 137 citations in OpenAlex.
- Cytotoxic CX3CR1+ Vδ1 T cells clonally expand in an interplay of CMV, microbiota, and HIV-1 persistence in people on antiretroviral therapy.PLoS pathogens · 2025Trial
- Human Cytomegalovirus Antigen Presentation by HLA-DR+ NKG2C+ Adaptive NK Cells Specifically Activates Polyfunctional Effector Memory CD4+ T Lymphocytes.Frontiers in immunology · 2019Trial
- Exploring the functions of NKG7 in CD4+ and CD8+ T cells during malaria.PLoS pathogens · 2026Article
- CD151 identifies a cytotoxic CD4 T cell population enriched in people with HIV that later develop cancer.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Mechanisms and Determinants of CMV Reactivation in Kidney Transplantation.International journal of molecular sciences · 2026Review
- Article
- Killer-cell immunoglobulin-like receptors define a potent effector program in human γδ T cells.JCI insight · 2026Article
- The AICL-KLRF1 axis supports CD4-CD8 T cell communication and cytokine competence in pre-exhausted CD8EMBO reports · 2026Article
- Cytomegalovirus-induced severe enterocolitis associated with ANCA-associated vasculitis and diffuse alveolar haemorrhage in a child: a diagnostic and therapeutic dilemma.BMC pediatrics · 2026Article
- Aging and vaccines: impact of immunosenescence and inflammaging in vaccine response.Frontiers in aging · 2026Review
- LANA-specific CD4Nature communications · 2025Article
- Guiding Antiviral Cell Therapy Approaches with an Online Resource of Clinically Scored Epitopes, T-Cell Receptors, and B-Cell Receptors.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2025Article
- Valaciclovir therapy for secondary suppression of immune response to herpesviruses: An exploratory study.PLoS pathogens · 2025Article
- Mapping CMV-related immune signatures in blood, aorta and perivascular mediastinal adipose tissue.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Article
- The immunomodulatory role of human cytomegalovirus in cancer in the era of checkpoint immunotherapy.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- The immune response to human cytomegalovirus: impact of age, co-morbidities and the significance of anti-viral activity assessment.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Long-persisting SARS-CoV-2 spike-specific CD4Nature communications · 2025Article
- Different CMV-specific effector T cell subtypes are associated with age, CMV serostatus, and increased systolic blood pressure.Immunity & ageing : I & A · 2025Article
- Adaptive immune responses against common viruses are sustained and functional in end-of-life patients.iScience · 2025Article
- Enhanced levels of IL-6 and PAI-1 and decreased levels of MMP-3 in cytomegalovirus seropositive patients with prior myocardial infarction.International journal of cardiology. Heart & vasculature · 2025Article
42 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
Cytomegalovirus (CMV) infection elicits a very strong and sustained intravascular T cell immune response which may contribute towards development of accelerated immune senescence and vascular disease in older people. Virus-specific CD8+ T cell responses have been investigated extensively through the use of HLA-peptide tetramers but much less is known regarding CMV-specific CD4+ T cells. We used a range of HLA class II-peptide tetramers to investigate the phenotypic and transcriptional profile of CMV-specific CD4+ T cells within healthy donors. We show that such cells comprise an average of 0.45% of the CD4+ T cell pool and can reach up to 24% in some individuals (range 0.01-24%). CMV-specific CD4+ T cells display a highly differentiated effector memory phenotype and express a range of cytokines, dominated by dual TNF-α and IFN-γ expression, although substantial populations which express IL-4 were seen in some donors. Microarray analysis and phenotypic expression revealed a profile of unique features. These include the expression of CX3CR1, which would direct cells towards fractalkine on activated endothelium, and the β2-adrenergic receptor, which could permit rapid response to stress. CMV-specific CD4+ T cells display an intense cytotoxic profile with high level expression of granzyme B and perforin, a pattern which increases further during aging. In addition CMV-specific CD4+ T cells demonstrate strong cytotoxic activity against antigen-loaded target cells when isolated directly ex vivo. PD-1 expression is present on 47% of cells but both the intensity and distribution of the inhibitory receptor is reduced in older people. These findings reveal the marked accumulation and unique phenotype of CMV-specific CD4+ T cells and indicate how such T cells may contribute to the vascular complications associated with CMV in older people.
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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.