ArticlePLoS pathogens2013
Multifunctional double-negative T cells in sooty mangabeys mediate T-helper functions irrespective of SIV infection.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- The Hitchhiker Guide to CD4Frontiers in immunology · 2021Pooled it
- Intact type I Interferon production and IRF7 function in sooty mangabeys.PLoS pathogens · 2013Trial
- Mendelian randomization and mediation analysis reveal the role of immune cells in the pathways between inflammatory factors and glioblastoma.The Journal of international medical research · 2025Article
- It's all in the gut: the central role of the gut and microbiome in preventing disease progression in simian immunodeficiency viruses infected African nonhuman primates.Current opinion in HIV and AIDS · 2025Review
- Causal relationship between inflammatory proteins, immune cells, and gout: a Mendelian randomization study.Scientific reports · 2024Article
- Article
- Cellular and Humoral Immune Responses to Vaccination for COVID-19 Are Negatively Impacted by Senescent T Cells: A Case Report.Vaccines · 2023Article
- Prolonged experimental CD4Nature communications · 2023Article
- CD3Frontiers in immunology · 2022Review
- Walk on the wild side: SIV infection in African non-human primate hosts-from the field to the laboratory.Frontiers in immunology · 2022Review
- Double Negative T Regulatory Cells: An Emerging Paradigm Shift in Reproductive Immune Tolerance?Frontiers in immunology · 2022Review
- Decreased CD73+ Double-Negative T Cells and Elevated Level of Soluble CD73 Correlated With and Predicted Poor Immune Reconstitution in HIV-Infected Patients After Antiretroviral Therapy.Frontiers in immunology · 2022Article
- Lost in Translation: Lack of CD4 Expression due to a Novel Genetic Defect.The Journal of infectious diseases · 2021Article
- Distinct CD4Frontiers in immunology · 2021Article
- HIV Infection and Persistence in Pulmonary Mucosal Double Negative T CellsJournal of virology · 2020Article
- Multivariate profiling of African green monkey and rhesus macaque T lymphocytes.Scientific reports · 2019Article
- Cytotoxic T Cell Functions Accumulate When CD4 Is Downregulated by CD4Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Potential Role of Vδ2Frontiers in immunology · 2017Article
- Induction of Unconventional T Cells by a Mutant Mycobacterium bovis BCG Strain Formulated in Cationic Liposomes Correlates with Protection against Mycobacterium tuberculosis Infections of Immunocompromised Mice.Clinical and vaccine immunology : CVI · 2016Article
- Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Studying SIV infection of natural host monkey species, such as sooty mangabeys, has provided insights into the immune changes associated with these nonprogressive infections. Mangabeys maintain immune health despite high viremia or the dramatic CD4 T cell depletion that can occur following multitropic SIV infection. Here we evaluate double-negative (DN)(CD3+CD4-CD8-) T cells that are resistant to SIV infection due to a lack of CD4 surface expression, for their potential to fulfill a role as helper T cells. We first determined that DN T cells are polyclonal and predominantly exhibit an effector memory phenotype (CD95+CD62L-). Microarray analysis of TCR (anti-CD3/CD28) stimulated DN T cells indicated that these cells are multifunctional and upregulate genes with marked similarity to CD4 T cells, such as immune genes associated with Th1 (IFNγ), Th2 (IL4, IL5, IL13, CD40L), Th17 (IL17, IL22) and TFH (IL21, ICOS, IL6) function, chemokines such as CXCL9 and CXCL10 and transcription factors known to be actively regulated in CD4 T cells. Multifunctional T-helper cell responses were maintained in DN T cells from uninfected and SIV infected mangabeys and persisted in mangabeys exhibiting SIV mediated CD4 loss. Interestingly, TCR stimulation of DN T cells from SIV infected mangabeys results in a decreased upregulation of IFNγ and increased IL5 and IL13 expression compared to uninfected mangabeys. Evaluation of proliferative capacity of DN T cells in vivo (BrDU labeling) indicated that these cells maintain their ability to proliferate despite SIV infection, and express the homeostatic cytokine receptors CD25 (IL2 receptor) and CD127 (IL7 receptor). This study identifies the potential for a CD4-negative T cell subset that is refractory to SIV infection to perform T-helper functions in mangabeys and suggests that immune therapeutics designed to increase DN T cell function during HIV infection may have beneficial effects for the host immune system.
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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.