ArticleJournal of virology2015
Cooperativity of HIV-Specific Cytolytic CD4 T Cells and CD8 T Cells in Control of HIV Viremia.
Article in Journal of virology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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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
54 citing papers in PubMed.
- Combined skin and muscle vaccination differentially impact the quality of effector T cell functions: the CUTHIVAC-001 randomized trial.Scientific reports · 2017Trial
- Long-term follow up of human T-cell responses to conserved HIV-1 regions elicited by DNA/simian adenovirus/MVA vaccine regimens.PloS one · 2017Trial
- Cytotoxic CD4Signal transduction and targeted therapy · 2026Review
- Cytotoxic CD4 T Cells: Dual Agents in HIV-1 Pathogenesis and Persistence.Current HIV/AIDS reports · 2026Review
- The Complex Dysregulations of CD4 T Cell Subtypes in HIV Infection.International journal of molecular sciences · 2024Review
- Immunotherapy-induced cytotoxic T follicular helper cells reduce numbers of retrovirus-infected reservoir cells in B cell follicles.PLoS pathogens · 2023Article
- Senescent T cells: Beneficial and detrimental roles.Immunological reviews · 2023Review
- Cytotoxic CD4Frontiers in immunology · 2023Review
- Cytotoxic CD4 T cells in the mucosa and in cancer.Frontiers in immunology · 2023Review
- Regulation of CD4 T Cell Responses by the Transcription Factor Eomesodermin.Biomolecules · 2022Review
- HIV-1-Infected CD4Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Article
- Highly dampened HIV-specific cytolytic effector T cell responses define viremic non-progression.Immunobiology · 2022Article
- Safety and durability of AGT103-T autologous T cell therapy for HIV infection in a Phase 1 trial.Frontiers in medicine · 2022Article
- T-Follicular-Like CD8Frontiers in immunology · 2022Article
- Functional Characteristics and Phenotypic Plasticity of CD57Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Article
- Review
- Diminished Peripheral CD29hi Cytotoxic CD4+ T Cells Are Associated With Deleterious Effects During SIV Infection.Frontiers in immunology · 2021Article
- Landscape of T Cells Transcriptional and Metabolic Modules During HIV Infection Based on Weighted Gene Co-expression Network Analysis.Frontiers in genetics · 2021Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
unlabelledCD4+ T cells play a pivotal role in the control of chronic viral infections. Recently, nontraditional CD4+ T cell functions beyond helper effects have been described, and a role for cytolytic CD4+ T cells in the control of HIV infection has been suggested. We define here the transcriptional, phenotypic, and functional profiles of HIV-specific cytolytic CD4+ T cells. Fluidigm BioMark and multiparameter flow cytometric analysis of HIV-specific cytolytic CD4+ T cells revealed a distinct transcriptional signature compared to Th1 CD4+ cells but shared similar features with HIV-specific cytolytic CD8+ T cells. Furthermore, HIV-specific cytolytic CD4+ T cells showed comparable killing activity relative to HIV-specific CD8+ T cells and worked cooperatively in the elimination of virally infected cells. Interestingly, we found that cytolytic CD4+ T cells emerge early during acute HIV infection and tightly follow acute viral load trajectory. This emergence was associated to the early viral set point, suggesting an involvement in early control, in spite of CD4 T cell susceptibility to HIV infection. Our data suggest cytolytic CD4+ T cells as an independent subset distinct from Th1 cells that show combined activity with CD8+ T cells in the long-term control of HIV infection. IMPORTANCE: The ability of the immune system to control chronic HIV infection is of critical interest to both vaccine design and therapeutic approaches. Much research has focused on the effect of the ability of CD8+ T cells to control the virus, while CD4+ T cells have been overlooked as effectors in HIV control due to the fact that they are preferentially infected. We show here that a subset of HIV-specific CD4+ T cells cooperate in the cytolytic control of HIV replication. Moreover, these cells represent a distinct subset of CD4+ T cells showing significant transcriptional and phenotypic differences compared to HIV-specific Th1 cells but with similarities to CD8+ T cells. These findings are important for our understanding of HIV immunopathology.
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