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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cells of the monocyte/macrophage lineage are the first targets of HIV-1 in patients and also serve as reservoirs for the virus during the course of infection. We investigated the effects of cell activation on early events of HIV-1 infection of monocyte-derived macrophages. Addition of LPS, a potent stimulator of macrophages, at the time of infection stimulated entry of HIV-1 into monocyte-derived macrophages, as judged by accumulation of early products of RT, but inhibited the synthesis of late RT products and strongly repressed nuclear import of the viral DNA, resulting in protection from infection. This effect was mediated by the CD14 receptor and involved activation of the p38 mitogen-activated protein kinase pathway. Disruption of this signaling pathway using a specific inhibitor of the p38 mitogen-activated protein kinase (SB203580) restored HIV-1 infection in the presence of LPS. These results suggest a novel view of the role of macrophage activation in anti-HIV responses of the immune system.
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PMID:Activation-induced resistance of human macrophages to HIV-1 infection in vitro. 988 13

Human immunodeficiency virus (HIV) infection causes dysregulation of surface phenotype, of accessory function and of cytokine production from peripheral blood mononuclear cells (PBMCs). As CD40 ligation induces several functional activities in these cells, this stimulation may partially mimic the situation occurring in vivo during an antigen-driven immune response. The aim of this study was to measure cytokine production and immunophenotypic changes induced by CD40 stimulation of PBMCs from HIV-positive patients. Under these experimental conditions, total and heterodimeric interleukin (IL)-12 production from PBMCs was similar, while IL-10 production was increased in HIV-positive patients compared with controls. On the contrary, CD40 ligation did not induce IL-15 production by PBMCs. Surface CD14 was down-modulated, as a consequence of CD40 stimulation, on monocytes from healthy controls but not on monocytes from HIV-positive patients. These data demonstrate that some of the CD40-mediated signals are disturbed in HIV-positive patients. These disturbances may contribute to the immune dysfunction seen in HIV infection.
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PMID:The effects of CD40 ligation on peripheral blood mononuclear cell interleukin-12 and interleukin-15 production and on monocyte CD14 surface antigen expression in human immunodeficiency virus-positive patients. 1010 46

We evaluated a flow cytometric (FCM) two-color immunophenotyping of CD3+/CD4+ T-helper and CD3+/CD8+ T-suppressor lymphocytes in whole blood samples from HIV-infected individuals using monoclonal antibody reagents from three different manufacturers. Lymphocytes were firstly determined using CD45/CD14 in association with a forward scatter/side scatter gating strategy. CD3+/CD4+ and CD3+/CD8+ were then determined and compared. Reagents from all manufacturers showed good separation of lymphocytes, monocytes and granulocytes with high purity and recovery. There was a good correlation of the percentage of CD3+/CD4+ and CD3+/CD8+ lymphocytes amongst each of the manufacturer's reagents, but the fluorescent intensities of positive cells were not the same. This difference can result in poor discrimination of positive and negative non CD3 cells leading to erroneous results.
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PMID:Evaluation of monoclonal antibody reagents from three different manufacturers using flow cytometric two-color immunophenotyping. 1021

To better understand the cutaneous immune response to Treponema pallidum, we performed an immunohistologic study of skin biopsies from a total of 11 patients with secondary syphilis; biopsies from five persons infected with HIV-1 were included in the analysis to assess at the tissue level the impact of concomitant HIV-1 infection on disease expression. In all of the biopsies, staining for HLA-DR, a marker for cellular activation, was observed among infiltrating leukocytes, dermal vascular endothelial cells, and keratinocytes. Infiltrating mononuclear cells stained positively for CD4 or CD8, with CD4+ cells always being in the majority. Surprisingly, most of the CD4+ cells had histiocytic, rather than lymphocytic, morphologic characteristics. Immunostaining for CD14 confirmed that these cells were monocytic in origin, whereas immunostaining for CD3 revealed that the lymphocytes were predominantly CD8+ cytotoxic T cells. B cells were not detected despite the presence of variable numbers of plasma cells in all specimens. By immunofluorescence, all of the specimens demonstrated perivascular deposition of immunoglobulins, complement, or fibrinogen; linear staining at the dermal-epidermal junction also was observed in most of the specimens. No differences in immunocytochemical or immunofluorescence staining patterns were observed between the specimens from patients who were HIV positive and patients who were HIV negative. In addition to providing a more precise definition of the infiltrating cells in syphilitic lesions, our results, taken as a whole, indicate that cellular immune processes are largely responsible for the development of cutaneous manifestations during syphilitic infection and that coinfection with HIV-1 has little discernible effect on the cutaneous response to T. pallidum.
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PMID:Secondary syphilis in persons infected with and not infected with HIV-1: a comparative immunohistologic study. 1053 71

Low levels of CD2 have been described on subsets of monocytes, macrophages, and dendritic cells. CD2 is expressed on about one-third of circulating monocytes, at levels one-half log lower than on T or NK cells, representing 2-4% of PBMC. FACS analysis of CD2+ and CD2- monocytes revealed no significant difference in the expression of adhesion molecules (CD11a/b/c), class II Ags (HLA-DR, -DQ, -DP), myeloid Ags (CD13, CD14, CD33), or costimulatory molecules (CD80, CD86). Freshly isolated CD2+ and CD2- monocytes were morphologically indistinguishable by phase contrast microscopy. However, scanning electron microscopy revealed large prominent ruffles on CD2+ monocytes in contrast to small knob-like projections on CD2- monocytes. After 2 days of culture, the CD2+ monocytes largely lost CD14 expression and developed distinct dendrites, whereas the CD2- monocytes retained surface CD14 and remained round or oval. Freshly isolated CD2+ monocytes were more potent inducers of the allogeneic MLR and more efficiently induced proliferation of naive T cells in the presence of HIV-1 gp120 than did CD2- monocytes. After culture in the presence of GM/CSF and IL-4, CD2+ monocytes were up to 40-fold more potent than monocyte-derived dendritic cells or CD2- monocytes at inducing allogeneic T cell proliferation. These findings suggest that circulating CD2+ and CD2- monocytes are dendritic cells and the precursors of macrophages, respectively. Thus, dendritic cells are far more abundant in the blood than previously thought, and they and precursors of macrophages exist in the circulation as phenotypically, morphologically, and functionally distinct monocyte populations.
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PMID:Circulating CD2+ monocytes are dendritic cells. 1057 Feb 78

Treponema pallidum, its membrane lipoproteins, and synthetic lipoprotein analogues (lipopeptides) were each examined to determine whether they induced CCR5 expression on human peripheral blood mononuclear cells (PBMC). Reverse transcription-polymerase chain reaction for CCR5 gene transcripts, macrophage inflammatory protein (MIP)-1beta binding assays, and flow cytometry revealed that either T. pallidum, a representative treponemal lipoprotein, or a corresponding synthetic lipopeptide induced CCR5 on CD14 monocytes but not on CD3 lymphocytes. CXCR4, the coreceptor for T cell-tropic strains of human immunodeficiency virus type 1 (HIV-1), was not induced on PBMC by treponemes or by lipoproteins or lipopeptides. Consistent with these findings, T. pallidum, lipoprotein, and synthetic lipopeptide all promoted the entry of a macrophage-tropic, but not a T cell-tropic, strain of HIV-1 into monocytes. These combined results imply that T. pallidum and its constituent lipoproteins likely induce the expression of CCR5 on macrophages in syphilitic lesions, thereby enhancing transmission of macrophage-tropic HIV-1.
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PMID:Virulent Treponema pallidum, lipoprotein, and synthetic lipopeptides induce CCR5 on human monocytes and enhance their susceptibility to infection by human immunodeficiency virus type 1. 1060 77

Monocytes represent a leukocyte subset that express high levels of CD14 on their surface (CD14-high). These cells play a critical role in the pathogenesis of HIV-1 infection. In the present study, we have identified a monocyte subset expressing an extremely low level of CD14 (CD14-low), and examined their susceptibility to HIV-1 infection. Phenotypic analysis by flow cytometry of these cells revealed a low level of CD4, but the absence of CD3, CD14, CD19, and CD83 surface markers. Both CD14-low and CD14-high cell populations expressed CD13 and CD33 markers on their surface, suggesting these cells to be of myeloid origin. Morphologically, CD14-low cells were indistinguishable from CD14-high cells. CD14-low cells were susceptible to infection with a monocytotropic strain of HIV-1 (HIVADA). However, like CD14-high monocytes, CD14-low cells could not be productively infected with a T cell tropic strain of HIV-1 (H9/HTLV(IIIB)). Similar to CD14-high monocytes, CD14-low cells were capable of inducing antigen-stimulated CD4+ T-cell proliferation. HIV-1 infection substantially reduced their ability to induce antigen-stimulated T-cell proliferation. These data indicate that CD14-low cells belong to the monocyte lineage and may play an important role in the immunopathogenesis of HIV-1 infection.
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PMID:HIV-1 infects and alters immune function of a monocyte subset expressing low CD14 surface phenotype. 1073 65

Data are limited regarding serum concentrations of soluble CD14 (sCD14), a marker of macrophage activation, in patients with active tuberculosis (TB) and during drug treatment. In this study, concentrations of sCD14 were measured in serum samples obtained from 105 African subjects who were categorized into one of four groups: persons with pulmonary TB alone (TB+HIV-, n = 30), pulmonary TB and HIV co-infection (TB+HIV+, n = 20), or HIV infection alone (TB-HIV+, n = 25), and healthy controls (TB-HIV-, n = 30). Mean total sCD14 was significantly increased in serum of patients with newly diagnosed pulmonary TB (mean = 6.6 g/ml, s.d. = 1.6 g/ml) compared with healthy controls (mean = 3.1 g/ml, s.d. = 0.6 g/ml; P < 0.0001), and this elevation comprised proportionate increases in the alpha (2.1-fold greater, P < 0.0001) and beta (2.0-fold greater, P < 0. 0001) forms of sCD14. Total sCD14 was also increased in serum of HIV-infected patients (mean = 4.1 g/ml, s.d. = 1.9 g/ml; P < 0.01), but the highest concentrations were observed in patients with pulmonary TB and HIV co-infection (mean = 8.7 g/ml, s.d. = 3.1 g/ml; P < 0.0001). Analysis of serum samples prospectively collected from TB+HIV-patients during the first 3 months of successful anti-TB treatment demonstrated steep reductions in mean concentrations of the acute-phase protein, C-reactive protein, and the soluble lymphocyte activation marker, sCD25. In contrast, levels of sCD14 increased during the first month of treatment and slowly declined thereafter. These data indicate that the serum concentration of sCD14 is not a sensitive index of response to anti-TB treatment and suggest that cellular activation resolves more slowly in the macrophage pool compared with the lymphocyte pool during anti-TB treatment.
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PMID:Elevated serum concentrations of soluble CD14 in HIV- and HIV+ patients with tuberculosis in Africa: prolonged elevation during anti-tuberculosis treatment. 1084 27

Parenchymal microglia are targets of HIV infection. We, as well as others, have used in vitro microglia culture systems to study the tropism and replication of HIV. Characterization of perivascular and parenchymal microglia surface markers in vivo, in vitro, and ex vivo, has led to the understanding that these cell populations are different, and data from both the HIV and SIV models support the hypothesis that they may play different roles in infection of the CNS. We determined that human adult parenchymal microglia cultured from temporal lobe tissue for use in HIV replication studies, were CD11c+, CD45+, CD68+, CD14- when cultured with standard serum/cytokine-supplemented media. To determine the influence of serum and cytokines on HIV replication in microglia, we designed a new protocol for culturing microglia, and compared the results obtained with this protocol with the standard approach previously described. Microglia cultured in the presence of a 'feeder' layer of glial cells and in the absence of serum and cytokines expressed the same surface markers as pure microglia (>95%) cultured in supplemented media. However, pure microglia cultured in the absence of both serum/cytokines supplements and other glial cells, did not have characteristic microglial morphology and did not support HIV replication to as high a level. Lastly, we determined that unlike monocytes, ex vivo parenchymal microglia were capable of supporting HIV replication.
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PMID:Characterization of cultured microglia that can be infected by HIV-1. 1087 66

The cellular entry of HIV is mediated by the specific interaction of viral envelope glycoproteins with the cell-surface marker CD4 and a chemokine receptor (CCR5 or CXCR4). Individuals with a 32-base-pair (bp) deletion in the CCR5 coding region, which results in a truncated peptide, show resistance to HIV-1 infection. This suggests that the downregulation of CCR5 expression on target cells may prevent HIV infection. Therefore, ribozymes that inhibit the CCR5 expression offer a novel approach for anti-HIV gene therapy. To assess the effect of an anti-CCR5 ribozyme (R5Rbz) on macrophage differentiation, CD34+ hematopoietic progenitor cells were transduced with a retroviral vector carrying RSRbz and allowed to differentiate in the presence of appropriate cytokines. R5Rbz-transduced CD34+ cells differentiated normally into mature macrophages that carried CD14 and CD4 surface markers, expressed the anti-CCR5 ribozyme, and showed significant resistance to viral infection upon challenge with the HIV-1 BaL strain. Using an in vivo thymopoiesis model, the effect of RSRbz on stem cell differentiation into thymocytes was evaluated by reconstituting SCID-hu mice thymic grafts with ribozyme-transduced CD34+ cells. FACS analysis of cell biopsies at 4 and 6 weeks postengraftment for HLA, CD4, and CD8 markers showed comparable levels of reconstitution and similar percentages of subpopulations of thymocytes between grafts receiving R5Rbz-transduced and control CD34+ cells. RT-PCR assays demonstrated the expression of the anti-CCR5 ribozyme in CD4+, CD8+, and CD4+/CD8+ thymocyte subsets derived from RSRbz-transduced CD34+ cells. These results indicate that anti-CCR5 ribozyme can be introduced into hematopoietic stem cells without adverse effects on their subsequent lineage-specific differentiation and maturation. The expression of anti-CCR5 ribozymes in HIV-1 target cells offers a novel gene therapy strategy to control HIV infection.
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PMID:Characterization of anti-CCR5 ribozyme-transduced CD34+ hematopoietic progenitor cells in vitro and in a SCID-hu mouse model in vivo. 1093 40


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