Influence of Plasma Viremia on Defects in Number and Immunophenotype of Blood Dendritic Cell Subsets in Human Immunodeficiency Virus 1–Infected Individuals

Department of Medicine, University of Colorado, Denver, Colorado, United States
The Journal of Infectious Diseases (Impact Factor: 6). 02/2003; 187(1):26-37. DOI: 10.1086/345957
Source: PubMed


Dendritic cells (DCs) are postulated to be involved in transmission of human immunodeficiency virus (HIV) type 1 to T cells
and in stimulation of HIV-1–specific cell-mediated immunity. Blood DCs have been categorized as myeloid (mDC) and plasmacytoid
(pDC) subsets, on the basis of differences in phenotype and function. Blood DC subset numbers and expression of costimulatory
molecules and HIV-1 coreceptors on DCs were measured in the blood of treated and untreated HIV-1–infected subjects and uninfected
control subjects. Absolute numbers of mDCs and pDCs were lower in HIV-1–infected subjects than in control subjects, most significantly
in those with active HIV-1 replication. Increased surface expression of costimulatory molecules was observed on both DC subsets
in subjects with HIV-1 viremia. Highly active antiretroviral therapy suppression of plasma viremia resulted in increases in
blood DC numbers and decreases in DC costimulatory molecule expression. These findings further define the impact of HIV-1
replication on blood DC subsets in vivo

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Available from: Samantha Mawhinney, Jan 11, 2016
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    • "In HIV infection it has been demonstrated a reduction in absolute number of mDC and pDC, especially in patients with active HIV-1 replication [3], suggesting a key role of DC in controlling viral load. Moreover the preserved functionality of pDC isolated from “elite controllers” may be one of the mechanisms involved in the control of HIV-1 viremia in these subjects [4]. "
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    ABSTRACT: NLRP3-inflammasome activation was evaluated in monocyte-derived dendritic cells (DC) obtained through IL-4 (IL4-DC) or IFN-alpha (IFN-DC) protocols and pulsed with chemically inactivated HIV-1. Inflammasome' genes expression and IL-1ss secretion were compared in DC isolated from 15 healthy subjects (HC) and 10 HIV-1 infected individuals (HIV+). Whether HIV was able to increased NLRP3-inflammasome genes expression and IL-1ss secretion in IL4-DC from HC, the induction of inflammasome appeared significantly reduced in IFN-DC from HC, suggesting a different responsive state of IFN-DC compared to IL4-DC. No inflammasome activation was observed in IL4-DC as well as in IFN-DC derived from HIV + subjects, confirming previous findings on "unresponsive" state of DC derived from HIV + possibly due to chronic inflammatory state of these individuals. Our results showed that IFN-alpha differently modulates inflammasome expression during monocytes-DC in vitro differentiation. These findings could be of interest considering the on-going research about DC manipulation and therapeutic strategies for HIV + involving DC-based immune-vaccines.
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    • "This includes low CD4 T cell counts, CD4 T cell expression of markers associated with activation and exhaustion [14], [30], as well as CD8 T cell activation [9], [10], [11], [12], [13], [14]. Likewise, the patterns of decreased levels of mDCs [31], [32], [33], Treg cells [34], [35] and iNKT cells [36], [37], [38], increased PD-1 expression on iNKT cells [39], as well as increased plasma levels of sCD14 [14], [40], in CVID patients are shared with HIV-1 infected patients. Interestingly, it was previously reported that CVID patients with lower naïve CD4 T cell levels display worse clinical scores [41], and, in line with the present data, that CVID patients display a pattern of L-selectin and CD38 expression on CD8 T cells similar to that observed in HIV-1 infected patients [42]. "
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    ABSTRACT: Common variable immunodeficiency (CVID) is characterized by defective B cell function, impaired antibody production, and increased susceptibility to bacterial infections. Here, we addressed the hypothesis that poor antibody-mediated immune control of infections may result in substantial perturbations in the T cell compartment. Newly diagnosed CVID patients were sampled before, and 6-12 months after, initiation of intravenous immunoglobulin (IVIg) therapy. Treatment-naïve CVID patients displayed suppressed CD4 T cell counts and myeloid dendritic cell (mDC) levels, as well as high levels of immune activation in CD8 T cells, CD4 T cells, and invariant natural killer T (iNKT) cells. Expression of co-stimulatory receptors CD80 and CD83 was elevated in mDCs and correlated with T cell activation. Levels of both FoxP3+ T regulatory (Treg) cells and iNKT cells were low, whereas soluble CD14 (sCD14), indicative of monocyte activation, was elevated. Importantly, immune reconstitution treatment with IVIg partially restored the CD4 T cell and mDC compartments. Treatment furthermore reduced the levels of CD8 T cell activation and mDC activation, whereas levels of Treg cells and iNKT cells remained low. Thus, primary deficiency in humoral immunity with impaired control of microbial infections is associated with significant pathological changes in cell-mediated immunity. Furthermore, therapeutic enhancement of humoral immunity with IVIg infusions alleviates several of these defects, indicating a relationship between poor antibody-mediated immune control of infections and the occurrence of abnormalities in the T cell and mDC compartments. These findings help our understanding of the immunopathogenesis of primary immunodeficiency, as well as acquired immunodeficiency caused by HIV-1 infection.
    Full-text · Article · Oct 2013 · PLoS ONE
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    • "In some, this decrease correlated with plasma viral load and was partially restored following HAART (Feldman et al., 2001; Soumelis et al., 2001; Barron et al., 2003). However, it remains unclear whether DC functions recover following suppressive HAART in HIV-infected children. "
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    ABSTRACT: Understanding the defects in innate immunity associated with perinatal HIV infection is prerequisite for the effective antiretroviral treatment. We therefore compared the innate immune response (Dendritic cell (DC) phenotype and function in peripheral blood by flow cytometry at baseline and 12 months in HIV infected children in order to determine the defect associated with perinatal HIV infection. As compared to controls patients had decreased numbers of total DC including plasmacytoid (p)DC and myeloid (m)DC and impaired function based on induction of maturation markers (CD83, CD80, CCR7) and cytokines TNF-α and IFN-α (exclusive to pDC) upon stimulation with TLR7/8 agonist Resiquimod. These abnormalities were evident in all three CD4 immune categories and persisted over 12 months; pDC function worsened in HIV+ children without treatment and improved slightly in those on HAART. In conclusion, a majority of perinatally HIV-infected older children without HAART remain clinically stable in the short term, but have demonstrable immunologic abnormalities indicative of defects in the innate immune system. Children initiated on HAART showed improvement in CD4 counts but didn't show improvement in DC function over the short term. This article is protected by copyright. All rights reserved.
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