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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: Women with bacterial vaginosis (BV) have a higher risk of HIV transmission but the cause of risk is unknown. Dendritic cells (DC) are implicated in transmission of HIV and we previously observed that DC mature when exposed to mucosal fluid from women with BV. We hypothesized that maturation of DC by BV mucosal fluid would enhance DC-mediated trans-infection of HIV. Monocyte-derived DC (MDDC) were treated with mucosal fluid, incubated with HIVBal, and HIV trans-infection was evaluated. While LPS-treated MDDC increased HIVBal trans-infection, BV fluid reduced trans-infection. HIVBal DNA levels in MDDC were not affected by BV fluid or LPS but productive infection of MDDC was decreased by LPS and BV fluid. Mucosal fluid from women with BV does not increase MDDC-mediated trans-infection suggesting that BV does not increase HIV susceptibility by increasing DC-mediated trans-infection. However, indirect effects of DC maturation on HIV transmission cannot be ruled out. [Copyright &y& Elsevier]

Abstract: T-regulatory cell (T-reg) frequency is increased in HIV infection and with aging. We evaluated the effect of age on total, memory and naïve T-reg percentages in untreated HIV infection. Older HIV+ subjects had a total T-reg percent that is 2.8% (p =0.02) higher than among younger HIV+, older HIV− and younger HIV− subjects. In HIV+ subjects, the total T-reg percentage is inversely correlated with the lymphocyte proliferative responses to tetanus (r =−0.45, p =0.002) and Candida (r =−0.43, p =0.003) antigens. Similar correlations were seen between memory T-reg percentages and the lymphocyte proliferative response to tetanus and Candida in HIV+ subjects. T-reg percentages did not correlate consistently with markers of immune activation. T-reg percentages are increased in the older HIV+ population and may play a role in the accelerated disease progression seen in older HIV-infected persons. [Copyright &y& Elsevier]

Abstract: The frequency, subsets and activation status of peripheral blood invariant NKT (iNKT) cells were evaluated in pulmonary tuberculosis (TB) patients and in chronically HIV-1-infected subjects. The absolute numbers of iNKT cells were significantly decreased in TB patients and in HIV-1+ individuals who were antiretroviral therapy naive or had detectable viremia despite receiving HAART. iNKT cell subset analysis demonstrated a decreased percentage of CD4+ iNKT cells in HIV-1+ subjects, and a decreased percentage of double negative iNKT cells in TB patients. Peripheral blood iNKT cells from HIV-1+ and TB patients had significantly increased expression of CD69, CD38, HLA-DR, CD16, CD56, and CD62L. The expression of CD25 was significantly increased only on iNKT cells from TB patients. These findings indicate that peripheral blood iNKT cells in these two chronic infections show an up-regulated expression of activation markers, suggesting their role in the immune response to infection. [Copyright &y& Elsevier]