ArticleJournal of immunology (Baltimore, Md. : 1950)2013
In vivo blockade of the PD-1 receptor suppresses HIV-1 viral loads and improves CD4+ T cell levels in humanized mice.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 106 citations in OpenAlex.
- Anti-PD-L1 antibody ASC22 in combination with a histone deacetylase inhibitor chidamide as a "shock and kill" strategy for ART-free virological control: a phase II single-arm study.Signal transduction and targeted therapy · 2024Trial
- Clinical Trial of the Anti-PD-L1 Antibody BMS-936559 in HIV-1 Infected Participants on Suppressive Antiretroviral Therapy.The Journal of infectious diseases · 2017Trial
- Interleukin-2-Mediated Engraftment of Human Peripheral Blood Mononuclear Cells in Immunodeficient Mice to Develop a Model of HIV Infection: New Criteria for Engraftment Monitoring.International journal of molecular sciences · 2026Article
- PD-L1 expression in schistosomal granuloma: an immunohistochemical study in urinary bladder schistosomiasis.Journal of clinical pathology · 2026Article
- Glycans on non-structural protein 1 prevent premature T-cell mediated dengue virus clearance.EMBO molecular medicine · 2025Article
- Acute HIV-1 Infection: Paradigm and Singularity.Viruses · 2025Review
- Influence of PD-1 and PD-1L Immune Exhaustion Receptors on Immune Reconstruction in People Living With HIV.Journal of immunology research · 2025Article
- Inhibition of SFTSV replication in humanized mice by a subcutaneously administered anti-PD1 nanobody.EMBO molecular medicine · 2024Article
- Examining Chronic Inflammation, Immune Metabolism, and T Cell Dysfunction in HIV Infection.Viruses · 2024Review
- The role of CD4MedComm · 2023Review
- Focus on T cell exhaustion: new advances in traditional Chinese medicine in infection and cancer.Chinese medicine · 2023Review
- NK cell subsets and dysfunction during viral infection: a new avenue for therapeutics?Frontiers in immunology · 2023Review
- Review
- Review
- So Pathogenic or So What?-A Brief Overview of SIV Pathogenesis with an Emphasis on Cure Research.Viruses · 2022Review
- Inhibitory immune checkpoint molecules and exhaustion of T cells in COVID-19.Physiological research · 2021Review
- Perspectives on Non-BLT Humanized Mouse Models for Studying HIV Pathogenesis and Therapy.Viruses · 2021Review
- PD-1 Blockade Restores the Proliferation of Peripheral Blood Lymphocyte and Inhibits Lymphocyte Apoptosis in a BALB/c Mouse Model of CP BVDV Acute Infection.Frontiers in immunology · 2021Article
- RanBP3 Regulates Proliferation, Apoptosis and Chemosensitivity of Chronic Myeloid Leukemia CellsFrontiers in oncology · 2021Article
- Long Non-coding RNA GAS5 Regulates T Cell Functions via miR21-Mediated Signaling in People Living With HIV.Frontiers in immunology · 2021Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The programmed death-1 (PD-1) pathway limits the function of virus-specific T cells during chronic infection. We previously showed that blockade of the PD-1 pathway increases HIV-1-associated T cell function in vitro. However, the effect of PD-1 blockade on HIV-1 disease progression in vivo has not been examined. As in humans, HIV-1-infected humanized BALB/c-Rag2(-/-)γc(-/-) (Rag-hu) mice express elevated levels of PD-1 on T cells during chronic infection. To examine the effect of PD-1 blockade on disease progression, Rag-hu mice with chronic HIV-1 infection were treated with a blocking mAb directed against programmed cell death-1 ligand-1, the ligand for PD-1. Programmed cell death-1 ligand-1-treated Rag-hu mice exhibited a progressive decrease in the HIV-1 plasma viral load, with a 7-fold decrease by day 7, a 20-fold decrease by day 14, a 178-fold decrease by day 21, and a 269-fold decrease by day 28 postinitiation of treatment. By day 7, the percentage of CD4(+) T cells was statistically higher in the treated compared with the untreated group, and this trend was sustained throughout the 28-d treatment period. Moreover, there was a strong inverse correlation between plasma viral load and the percentage of both CD4(+) (r = -0.66; p < 0.0001) and CD8(+) (r = -0.64; p < 0.0001) T cells in the treated mice but not the untreated mice. This study provides "proof of concept" that humanized mice can be used to examine the effects of immunotherapeutic interventions on HIV-1 infection. Furthermore, to our knowledge, these data demonstrate for the first time that blockade of the PD-1 pathway reduces HIV-1 viral loads.
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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.