ArticlePloS one2014
Regulatory B cells inhibit cytotoxic T lymphocyte (CTL) activity and elimination of infected CD4 T cells after in vitro reactivation of HIV latent reservoirs.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
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- Suppressive mechanisms of regulatory B cells in mice and humans.International immunology · 2023Article
- Distinct immunological and molecular signatures underpinning influenza vaccine responsiveness in the elderly.Nature communications · 2022Article
- Regulatory Role of B Cells and Its Subsets in Hepatitis E Virus Infection.BioMed research international · 2022Article
- Antibody-independent functions of B cells during viral infections.PLoS pathogens · 2021Review
- Immunosuppressive Mechanisms of Regulatory B Cells.Frontiers in immunology · 2021Review
- The balancing act: Immunology of leishmaniosis.Research in veterinary science · 2020Review
- Antisense of survivin inhibits cervical cancer growth in mice.Archives of medical science : AMS · 2019Article
- Elevated numbers of PD-L1 expressing B cells are associated with the development of AIDS-NHL.Scientific reports · 2019Article
- Analysis of the dysregulation between regulatory B and T cells (Breg and Treg) in human immunodeficiency virus (HIV)-infected patients.PloS one · 2019Article
- Treatment Intensification in HIV-Infected Patients Is Associated With Reduced Frequencies of Regulatory T Cells.Frontiers in immunology · 2018Article
- B Cell Requirement for Robust Regulatory T Cell Responses to Friend Retrovirus Infection.mBio · 2017Article
- B cell regulation in cancer and anti-tumor immunity.Cellular & molecular immunology · 2017Review
- Human regulatory B cells in health and disease: therapeutic potential.The Journal of clinical investigation · 2017Review
- Programmed cell death 1 correlates with the occurrence and development of MG63 osteosarcoma.Oncology letters · 2016Article
- Accumulation of CD5Clinical and experimental medicine · 2016Article
- B Cell Responses Associated with Vaccine-Induced Delayed SIVmac251 Acquisition in Female Rhesus Macaques.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- The expanding family of regulatory B cells.International immunology · 2015Review
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
During HIV infection, IL-10/IL-10 receptor and programmed death-1 (PD-1)/programmed death-1-ligand (PD-L1) interactions have been implicated in the impairment of cytotoxic T lymphocyte (CTL) activity. Despite antiretroviral therapy (ART), attenuated anti-HIV CTL functions present a major hurdle towards curative measures requiring viral eradication. Therefore, deeper understanding of the mechanisms underlying impaired CTL is crucial before HIV viral eradication is viable. The generation of robust CTL activity necessitates interactions between antigen-presenting cells (APC), CD4+ and CD8+ T cells. We have shown that in vitro, IL-10hiPD-L1hi regulatory B cells (Bregs) directly attenuate HIV-specific CD8+-mediated CTL activity. Bregs also modulate APC and CD4+ T cell function; herein we characterize the Breg compartment in uninfected (HIVNEG), HIV-infected "elite controllers" (HIVEC), ART-treated (HIVART), and viremic (HIVvir), subjects, and in vitro, assess the impact of Bregs on anti-HIV CTL generation and activity after reactivation of HIV latent reservoirs using suberoylanilide hydroxamic acid (SAHA). We find that Bregs from HIVEC and HIVART subjects exhibit comparable IL-10 expression levels significantly higher than HIVNEG subjects, but significantly lower than HIVVIR subjects. Bregs from HIVEC and HIVART subjects exhibit comparable PD-L1 expression, significantly higher than in HIVVIR and HIVNEG subjects. SAHA-treated Breg-depleted PBMC from HIVEC and HIVART subjects, displayed enhanced CD4+ T-cell proliferation, significant upregulation of antigen-presentation molecules, increased frequency of CD107a+ and HIV-specific CD8+ T cells, associated with efficient elimination of infected CD4+ T cells, and reduction in integrated viral DNA. Finally, IL-10-R and PD-1 antibody blockade partially reversed Breg-mediated inhibition of CD4+ T-cell proliferation. Our data suggest that, possibly, via an IL-10 and PD-L1 synergistic mechanism; Bregs likely inhibit APC function and CD4+ T-cell proliferation, leading to anti-HIV CTL attenuation, hindering viral eradication.
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