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Abstract: The programmed death (PD)-1 interacts with its ligand (PDL-1) delivering a negative signal to T cells. During human immunodeficiency virus (HIV)-1 infection PD-1 and PDL-1 expressions are increased. Here we show that monocytes and CCR5+ T cells of HIV-uninfected donors upregulated PDL-1 upon in vitro exposure to HIV. HIV-induced PDL-1 required interferon (IFN)-α, but not IFN-γ, production. Inhibition of endocytosis, required for HIV-induced IFN-α production, prevented PDL-1 upregulation. IFN-α-inducing Toll-like receptor (TLR) agonists increased PDL-1 on monocytes and CCR5+ T cells. CD80 and CD86 were also increased on monocytes and CCR5+ T cells after HIV exposure, but only CD80 was IFN-α-dependent. IFN-α-receptor subunit 2 (IFNAR2), was expressed only by CCR5+ T cells and monocytes, explaining why these leukocytes responded to HIV-induced IFN-α. Finally, T cell proliferation was improved by PDL-1 blockade in HIV-treated PBMC. In the setting of HIV infection, IFN-α may negatively affect T cell responses by inducing PDL-1. [Copyright &y& Elsevier]

Highly active antiretroviral therapy (HAART) for the treatment of HIV infection sustains viral suppression and increases CD4 + T cells in HIV patients. However, in 10–25% of subjects, known as immunological non-responders (INRs), HAART does not increase CD4 count. We investigated a potential role for galectin-9 and TIM-3 in INRs as galectin-9 and TIM-3 have been described to modulate NK and T cell function. PBMCs were isolated from healthy controls, HIV immunological responders (IRs, > 350 CD4 + cells/mm 3 ) and HIV INRs (< 350 CD4 + cells/mm 3 ) and TIM-3 and galectin-9 expressions on NK cell subsets and CD4 + T cells were assessed. HIV INRs and HIV IRs showed increased galectin-9 expression on CD16 − CD56 bright and CD16 + CD56 + NK cells and CD4 + T cells. Only HIV INRs showed a reduced frequency of TIM-3-expressing CD16 + CD56 + , CD16 + CD56 − and CD4 + cells, which correlated with low peripheral CD4 counts. These data suggest that TIM-3 expression may be characteristic for HIV INRs. [ABSTRACT FROM AUTHOR]

Abstract: Dendritic cells (DC) at mucosal surfaces mature when exposed to “danger” signals such as LPS. Bacterial vaginosis (BV) is a prevalent alteration of the vaginal bacterial flora associated with preterm childbirth and increased risk for HIV acquisition. We examined the effect of mucosal fluid from women with BV or healthy flora on DC function. IL-12, IL-23 and p40 production by monocyte-derived dendritic cells (MDDC) were all induced by BV samples. Activation/maturation markers HLA-DR, CD40 and CD83 on MDDC incubated with BV CVL were also induced. BV CVL also decreased the endocytic ability of MDDC and increased proliferation of T cells in allogeneic MLR. Plasmacytoid dendritic cell (pDC) CD86 expression was induced by BV CVL. Healthy flora CVL had little effect in any of the tests. This study suggests that BV, but not healthy flora, affects local dendritic cell function in vivo suggesting a mechanism through which BV affects mucosal immunity. [Copyright &y& Elsevier]