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

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.