ArticlePLoS pathogens2013
Combining regulatory T cell depletion and inhibitory receptor blockade improves reactivation of exhausted virus-specific CD8+ T cells and efficiently reduces chronic retroviral loads.
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 51 papers.
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Who cites it
51 citing papers in PubMed, 68 citations in OpenAlex.
- Serum sCD25 predicts mortality and reflects IL-2-driven dysregulation of CD4⁺CD25⁺ T cells in severe fever with thrombocytopenia syndrome.Tropical medicine and health · 2026Article
- Regulatory T cells restrain IL-15-mediated cytotoxic and bystander T cell activity in mucosal tissue without compromising antigen-driven memory.bioRxiv : the preprint server for biology · 2026Article
- Renal allograft interstitial fibrosis: multicellular interactions and therapeutic strategies.Frontiers in immunology · 2026Review
- PD-1 knockout on cytotoxic primary murine CD8Frontiers in immunology · 2024Article
- Regulatory T cells suppress the motility of cytotoxic T cells in Friend retrovirus-infected mice.JCI insight · 2023Article
- The mouse resource at National Resource Center for Mutant Mice.Mammalian genome : official journal of the International Mammalian Genome Society · 2022Review
- Development and Characterization of a Nanobody against Human T-Cell Immunoglobulin and Mucin-3.Computational and mathematical methods in medicine · 2022Article
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- Immunotherapy With Interferon α11, But Not Interferon Beta, Controls Persistent Retroviral Infection.Frontiers in immunology · 2021Article
- Combination immunotherapy with anti-PD-L1 antibody and depletion of regulatory T cells during acute viral infections results in improved virus control but lethal immunopathology.PLoS pathogens · 2020Article
- Friend retrovirus studies reveal complex interactions between intrinsic, innate and adaptive immunity.FEMS microbiology reviews · 2019Review
- Chronic retroviral infection of mice promotes tumor development, but CD137 agonist therapy restores effective tumor immune surveillance.Cancer immunology, immunotherapy : CII · 2019Article
- Article
- FcγR-Binding Is an Important Functional Attribute for Immune Checkpoint Antibodies in Cancer Immunotherapy.Frontiers in immunology · 2019Review
- The Era of Immune Checkpoint Therapy: From Cancer to Viral Infection-A Mini Comment on the 2018 Medicine Nobel Prize.Virologica Sinica · 2018Article
- Cytotoxic CD8Brain pathology (Zurich, Switzerland) · 2018Article
- Regulatory T cells in retroviral infections.PLoS pathogens · 2018Review
- Induction of Type I Interferons by Therapeutic Nanoparticle-Based Vaccination Is Indispensable to Reinforce Cytotoxic CD8Frontiers in immunology · 2018Article
- Hepatitis B Virus-Specific CD8+ T Cells Maintain Functional Exhaustion after Antigen Reexposure in an Acute Activation Immune Environment.Frontiers in immunology · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic infections with human viruses, such as HIV and HCV, or mouse viruses, such as LCMV or Friend Virus (FV), result in functional exhaustion of CD8(+) T cells. Two main mechanisms have been described that mediate this exhaustion: expression of inhibitory receptors on CD8(+) T cells and expansion of regulatory T cells (Tregs) that suppress CD8(+) T cell activity. Several studies show that blockage of one of these pathways results in reactivation of CD8(+) T cells and partial reduction in chronic viral loads. Using blocking antibodies against PD-1 ligand and Tim-3 and transgenic mice in which Tregs can be selectively ablated, we compared these two treatment strategies and combined them for the first time in a model of chronic retrovirus infection. Blocking inhibitory receptors was more efficient than transient depletion of Tregs in reactivating exhausted CD8(+) T cells and reducing viral set points. However, a combination therapy was superior to any single treatment and further augmented CD8(+) T cell responses and resulted in a sustained reduction in chronic viral loads. These results demonstrate that Tregs and inhibitory receptors are non-overlapping factors in the maintenance of chronic viral infections and that immunotherapies targeting both pathways may be a promising strategy to treat chronic infectious diseases.
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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.