Analysis of the dysregulation between regulatory B and T cells (Breg and Treg) in human immunodeficiency virus (HIV)-infected patients

PLoS One. 2019 Mar 27;14(3):e0213744. doi: 10.1371/journal.pone.0213744. eCollection 2019.

Abstract

This study examines the relationship between regulatory B (Breg) and T (Treg) compartments, which play crucial roles in the maintenance of immune homeostasis in the context of HIV. Using flow cytometry, the phenotypes of different Breg and Treg subsets from HIV-infected and healthy individuals were analyzed, along with the suppressive capacity of Breg. Peripheral blood samples of thirteen HIV+ treatment-naïve individuals, fourteen treated-HIV+ individuals with undetectable viral load and twelve healthy individuals were analyzed. The absolute counts of Breg and Treg subsets were decreased in HIV+ treatment-naïve individuals in comparison to treated-HIV+ and healthy individuals. Interestingly, correlations between Breg subsets (CD24hiCD27+ and PD-L1+ B cells) and IL-10-producing Breg observed in healthy individuals were lost in HIV+ treatment-naïve individuals. However, a correlation between frequencies of CD24hiCD38hi or TIM-1+-Breg subsets and Treg was observed in HIV+ treatment-naïve individuals and not in healthy individuals. Therefore, we hypothesized that various Breg subsets might have different functions during B and T-cell homeostasis during HIV-1 infection. In parallel, stimulated Breg from HIV-infected treatment-naïve individuals presented a decreased ability to suppress CD4+ T-cell proliferation in comparison to the stimulated Breg from treated-HIV+ or healthy individuals. We demonstrate a dysregulation between Breg and Treg subsets in HIV-infected individuals, which might participate in the hyper-activation and exhaustion of the immune system that occurs in such patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • B-Lymphocyte Subsets / cytology
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / metabolism
  • B-Lymphocytes, Regulatory / cytology
  • B-Lymphocytes, Regulatory / immunology
  • B-Lymphocytes, Regulatory / metabolism*
  • Case-Control Studies
  • Cell Proliferation
  • Female
  • HIV / isolation & purification
  • HIV / physiology
  • HIV Infections / immunology
  • HIV Infections / pathology*
  • Humans
  • Interleukin-10 / metabolism
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Phenotype
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • Viral Load

Substances

  • Interleukin-10

Grants and funding

This work was partially supported by the Ministry of Economy and Competitiveness ISCIII-FIS grants PI12/01763, PI12/00934 and PI15/00923, co-financed by ERDF (FEDER) Funds from the European Commission, “A way of making Europe”. This work was also supported by the internal grant from the Research Health Institute Gregorio Marañón (IiSGM; grant II-PI-MP-2018). J.L-A. was supported by a Grant from IiSGM. A.P-S and V. P-F were supported by the Youth Employment Program co-financed by the Madrid community and FEDER Founds (PEJ15-BIO-TL-0094, PEJ15-BIO-TL0373, respectively). C.G. was supported by the Spanish AIDS Research Network. R.C-R was supported by “Miguel Servet” program (CPII13/00033), and M.P by the Spanish MICINN through the Ramón y Cajal (RYC-2009-05486). All this work was performed in the Laboratorio de Inmuno-Biología Molecular (HGUG and IiSGM) lead by M-A.M-F. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.