ArticleJournal of immunology (Baltimore, Md. : 1950)2011
HIV-mediated phosphatidylinositol 3-kinase/serine-threonine kinase activation in APCs leads to programmed death-1 ligand upregulation and suppression of HIV-specific CD8 T cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- HIV-Induced Apoptosis: Host Defense and Viral Strategy.Biology · 2025Review
- An immune-related signature based on molecular subtypes for predicting the prognosis and immunotherapy efficacy of hepatocellular carcinoma.Frontiers in immunology · 2025Article
- Interleukin-32: a Pandora's box in human immunodeficiency virus infection.Frontiers in immunology · 2025Review
- PD-L1 Expression Is Increased in LPS-Induced Acute Respiratory Distress Syndrome by PI3K-AKT-Egr-1/C/EBPδ Signaling Pathway.Inflammation · 2024Article
- Dysfunction and regulatory interplay of T and B cells in chronic hepatitis B: immunotherapy and emerging antiviral strategies.Frontiers in cellular and infection microbiology · 2024Review
- Focus on T cell exhaustion: new advances in traditional Chinese medicine in infection and cancer.Chinese medicine · 2023Review
- Generation, secretion and degradation of cancer immunotherapy target PD-L1.Cellular and molecular life sciences : CMLS · 2022Review
- Combined treatment with anti-PSMA CAR NK-92 cell and anti-PD-L1 monoclonal antibody enhances the antitumour efficacy against castration-resistant prostate cancer.Clinical and translational medicine · 2022Article
- CounterAKTing HIV: Toward a "Block and Clear" Strategy?Frontiers in cellular and infection microbiology · 2022Review
- β-Glucan Combined With PD-1/PD-L1 Checkpoint Blockade for Immunotherapy in Patients With Advanced Cancer.Frontiers in pharmacology · 2022Article
- Perspectives on immune checkpoint ligands: expression, regulation, and clinical implications.BMB reports · 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
- Comparison of miRNA Expression Profiles between HIV-1 and HIV-2 Infected Monocyte-Derived Macrophages (MDMs) and Peripheral Blood Mononuclear Cells (PBMCs).International journal of molecular sciences · 2020Article
- Humanized Mice as an Effective Evaluation System for Peptide Vaccines and Immune Checkpoint Inhibitors.International journal of molecular sciences · 2019Review
- Recent Findings in the Regulation of Programmed Death Ligand 1 Expression.Frontiers in immunology · 2019Review
- Regulation and Function of the PD-L1 Checkpoint.Immunity · 2018Review
- Article
- Inflammatory cytokines IL-17 and TNF-α up-regulate PD-L1 expression in human prostate and colon cancer cells.Immunology letters · 2017Article
- Posttranscriptional Control of PD-L1 Expression by 17β-Estradiol via PI3K/Akt Signaling Pathway in ERα-Positive Cancer Cell Lines.International journal of gynecological cancer : official journal of the International Gynecological Cancer Society · 2017Article
- Role of PD-1 co-inhibitory pathway in HIV infection and potential therapeutic options.Retrovirology · 2015Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Recent evidence demonstrates that HIV-1 infection leads to the attenuation of cellular immune responses, which has been correlated with the increased expression of programmed death (PD)-1 on virus-specific CD8(+) T cells. PD-1 is induced upon T cell activation, and its prolonged expression facilitates CD8(+) T cell inhibitory signals when bound to its B7 family ligands, PD-ligand (L)1/2, which are expressed on APCs. Importantly, early reports demonstrated that blockade of the PD-1/PD-L interaction by Abs may help to counter the development of immune exhaustion driven by HIV viral persistence. To better understand the regulation of the PD-1 pathway during HIV infection, we examined the ability of the virus to induce PD-L expression on macrophages and dendritic cells. We found a direct relationship between the infection of APCs and the expression of PD-L1 in which virus-mediated upregulation induced a state of nonresponsiveness in uninfected HIV-specific T cells. Furthermore, this exhaustion phenotype was revitalized by the blockade of PD-L1, after which T cells regained their capacity for proliferation and the secretion of proinflammatory cytokines IFN-γ, IL-2, and IL-12 upon restimulation. In addition, we identify a critical role for the PI3K/serine-threonine kinase signaling pathway in PD-L1 upregulation of APCs by HIV, because inhibition of these intracellular signal transducer enzymes significantly reduced PD-L1 induction by infection. These data identify a novel mechanism by which HIV exploits the immunosuppressive PD-1 pathway and suggest a new role for virus-infected cells in the local corruption of immune responses required for viral suppression.
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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.