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

The role of exogenous stimulation of CD40 by CD40 ligand (CD40L) in dendritic cell (DC) maturation, CC-chemokine production, and CCR5 receptor expression was examined using a soluble trimeric CD40L agonist protein (CD40LT). Stimulation of monocyte-derived DCs with CD40LT enhanced the production of the CC-chemokines macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, and RANTES and diminished surface expression of CCR5. Based on these findings, the functional role of CD40LT stimulation on the ability of DCs to replicate and transmit HIV viral infection was studied. The addition of CD40LT to cocultures of naive CD4+ T cells and autologous DCs (T/DC) infected with the macrophage-tropic isolate, HIVBaL, caused a striking reduction in reverse transcriptase (RT) activity after 10 and 14 days of culture. The addition of a mixture of Abs against CC-chemokines abrogated the decrease in RT activity, demonstrating that the inhibitory effect mediated by CD40LT was CC-chemokine-dependent. In contrast, the presence of CD40LT in T/DC cocultures infected with the T cell-tropic isolate, HIV IIIB, caused an increase in RT activity that was CC-chemokine-independent. Of note, CD40LT stimulation also inhibited RT activity in cultures containing macrophage-tropic virus (HIVBaL)-infected DC only. However, in contrast to the results seen in the T/DC cocultures, CD40LT stimulation inhibited RT activity in cultures of DCs alone in a CC-chemokine-independent manner. Together, these results show that CD40LT stimulation of DCs suppresses HIV replication and transmission to CD4+ T cells by two potentially different mechanisms.
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PMID:Differential effects of CD40 ligand/trimer stimulation on the ability of dendritic cells to replicate and transmit HIV infection: evidence for CC-chemokine-dependent and -independent mechanisms. 1009 34

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

CD43/leukosialin is a major sialoglycoprotein of the dendritic cell (DC) surface, which can regulate cell adhesion and has the potential to mediate cell activation signals. Monocyte-derived DC transiently incubated with the anti-CD43 mAb, MEM-59, or with F(ab')2 fragments, but not with monovalent Fab fragments or control IgG, 24 h later showed increased levels of membrane HLA-DR, CD54, CD40, CD80, CD86, and CD83. In parallel, CD43 cross-linking induced synthesis and release of IL-1beta, IL-6, TNF-alpha, IL-12, and IL-10. CD43 ligation inhibited the endocytic activity of DC, and enhanced the capacity of DC to stimulate T cell proliferation in the primary allogeneic and autologous MLR assay. In addition, anti-CD43-treated DC were less efficient at presenting native HIV-1 reverse transcriptase to a specific CD4+ T cell clone, whereas presentation of the reverse transcriptase 55-72 peptide to the same clone was increased. Finally, MEM-59 or its F(ab')2 fragments elicited a rise in intracellular free calcium and tyrosine phosphorylation of a 25-kDa protein in DC. The results thus indicate that CD43 cross-linking with specific ligands induces activation and functional maturation of DC.
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PMID:Cross-linking of membrane CD43 mediates dendritic cell maturation. 1035 44

Critical steps of B cell differentiation occur within lymphoid organs that are also major sites of HIV-1 replication. Because Tat can be released by infected cells, we investigated whether extracellular HIV-1 Tat modulates cell proliferation of B cells at critical stages of their differentiation. Here we show that extracellular Tat inhibited the proliferation of B cell receptor-triggered naive and memory B cells by >80% but had no effect on their CD40 mAb and IL-4-mediated proliferation. In striking contrast, Tat doubled the germinal center B cell proliferation induced by CD40 mAb and IL-4. These effects were dose dependent and required the addition of Tat at the initiation of the culture, suggesting that Tat acts on early stages of cell cycle progression. By its effects on B cell subsets, Tat might directly affect the normal B cell differentiation process in HIV-positive patients and favor the occurrence of AIDS-associated B cell lymphomas.
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PMID:Cutting edge: HIV-1 Tat protein differentially modulates the B cell response of naive, memory, and germinal center B cells. 1041 4

During HIV infection various cytokines are overproduced in early stages, whereas in advanced disease cytokines of the T helper 1 type (e.g. interferon-gamma (IFN-gamma)) are selectively deficient. During antigenic stimulation, the production of type-1 cytokines is enhanced by IL-12, secreted by antigen-presenting cells (APC) after their interaction with activated CD4 T cells. Two factors are essential in this process: priming APC with IFN-gamma and triggering the CD40 receptor on APC by CD40 ligand (CD40L). In view of the importance of this pathway, we compared its regulation in HIV-infected and control subjects. After cross-linking of the T cell receptor (TCR)/CD3 complex, the proportional expression of CD40L was similar on CD4+ T cells from controls and from patients with high circulating CD4 T counts (> 500/microl), but CD40L up-regulation was significantly reduced in patients with more advanced disease. Simultaneous triggering of the costimulatory receptor CD28 on T cells through its natural ligand CD80 partly corrected the CD40L defect in patients with intermediate CD4 T counts (200-500), but not in AIDS patients. Early production of IFN-gamma was preserved in lymphocytes from HIV+ patients. The expression of CD40 on peripheral monocytes from HIV+ subjects was increased in a disease stage-related fashion. Stimulation of mononuclear cells through cell-bound CD40L and soluble IFN-gamma induced significantly higher IL-12 in cultures from patients with > 200 circulating CD4 T cells, whereas IL-12 production was marginally decreased in cultures from patients with < 200 CD4 T cells, compared with healthy control cultures. In conclusion, our data suggest that impaired CD40L induction on CD4 T cells contributes to deficient type-1 responses through decreased IL-12 production in AIDS infection, whereas enhanced CD40-mediated IL-12 production in less advanced stages might contribute to increased levels of various cytokines in early disease
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PMID:Decreased CD40 ligand induction in CD4 T cells and dysregulated IL-12 production during HIV infection. 1044 66

Human immunodeficiency virus type 1 (HIV-1) replicates primarily in lymphoid tissues where it has ready access to activated immune competent cells. We used one of the major pathways of immune activation, namely, CD40-CD40L interactions, to study the infectability of B lymphocytes isolated from peripheral blood mononuclear cells. Highly enriched populations of B lymphocytes generated in the presence of interleukin-4 and oligomeric soluble CD40L upregulated costimulatory and activation markers, as well as HIV-1 receptors CD4 and CXCR4, but not CCR5. By using single-round competent luciferase viruses complemented with either amphotropic or HIV-derived envelopes, we found a direct correlation between upregulation of HIV-1 receptors and the susceptibility of the B lymphocytes to infection with dual-tropic and T-tropic strains of HIV-1; in contrast, cells were resistant to M-tropic strains of HIV-1. HIV-1 envelope-mediated infection was completely abolished with either an anti-CD4 monoclonal antibody or a peptide known to directly block CXCR4 usage and partially blocked with stromal cell-derived factor 1, all of which had no effect on the entry of virus pseudotyped with amphotropic envelope. Full virus replication kinetics confirmed that infection depends on CXCR4 usage. Furthermore, productive cycles of virus replication occurred rapidly yet under most conditions, without the appearance of syncytia. Thus, an activated immunological environment may induce the expression of HIV-1 receptors on B lymphocytes, priming them for infection with selective strains of HIV-1 and allowing them to serve as a potential viral reservoir.
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PMID:CD40-Mediated induction of CD4 and CXCR4 on B lymphocytes correlates with restricted susceptibility to human immunodeficiency virus type 1 infection: potential role of B lymphocytes as a viral reservoir. 1048 44

We have developed a method for isolating and characterizing pigtailed macaque dendritic cells (DCs) generated from CD34(+) bone marrow (BM) progenitors based on methods previously developed for isolating human DCs. Macaque DCs displayed a characteristic morphology and were potent stimulators of allogeneic T cell proliferation. They expressed a set of DC-associated markers, such as MHC class II, CD1a, CD4, CD11a, CD40, CD58, CD80, CD83, CD86, and CXCR4. Macaque DCs, as well as peripheral blood CD4(+) T cells, were highly susceptible to HIV-2 infection, as detected by DNA-PCR. The expression of HIV-2 in macaque DCs was downregulated by treatment with the beta-chemokine RANTES. Macaque DCs will be useful for defining the in vivo role of DCs in HIV pathogenesis and for optimizing and testing peptide-DC vaccines or tolerizing regimens.
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PMID:Isolation and characterization of macaque dendritic cells from CD34(+) bone marrow progenitors. 1048 53

Dendritic cells (DC) have been implicated in the initial selection for macrophage-tropic HIV-1 during transmission and in the generation of high-level virus replication during interactions with CD4 T cells. The role of DC as viral reservoirs and the extent of productive infection is unclear, but the ability to generate large numbers of DC from blood monocytes has produced a tractable model for study of DC-HIV-1 interactions. When cultured in granulocyte-macrophage colony stimulating factor and IL-4, sorted CD14+ monocytes rapidly lost phagocytic function for both 93 nm and 977 nm latex particles and developed the surface markers and function of DC. After 7 days, when returned to medium containing human serum without cytokines, some monocyte-derived dendritic cells (MDDC) became adherent, but retained the costimulatory markers CD80 and CD86 and continued to express CD83 and CD40. The MDDC stimulated allogeneic CD4 T cells, did not express new macrophage markers and remained non-phagocytic. With or without TNF-alpha, MDDC generated in cytokines were infected by macrophage and T cell-tropic virus and produced higher reverse transcriptase levels than did the autologous monocyte-derived macrophages (MDM). When added to T cells, the infected MDDC were able to infect T cells with a wider range of viral isolates than were MDM.
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PMID:Monocyte-derived dendritic cells as a model for the study of HIV-1 infection: productive infection and phenotypic changes during culture in human serum. 1054 Feb 11

CD40 can participate in inflammatory processes after binding its cognate ligand (CD40L). We found that fetal human astrocytes constitutively express CD40 mRNA and protein. Upon incubating cultures with proinflammatory cytokines (TNF-alpha, IL-1beta and IFN-gamma) or with lipopolysaccharide (LPS), CD40 expression was increased. No change in CD40 expression was noted in astrocyte cultures incubated with IL-6, HIV or gp41. Astrocytes also showed increased release of proinflammatory cytokines TNF-alpha, IL-1beta and IL-6 after incubation with CD40L peptide. These observations suggest a role for CD40 in central nervous system (CNS) inflammation and that CD40/CD40L autocrine or paracrine pathways may mediate this role.
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PMID:Cytokine regulation of CD40 expression in fetal human astrocyte cultures. 1058 Aug 8

Increased levels of serum IgE have been described in HIV-1 infection; however, mechanisms implicated in this immunoglobulin production remain unknown. In this study, we demonstrate that in vitro infection of human peripheral blood mononuclear cells (PBMCs) by HIV-1 monocytotropic (Ba-L) or lymphocytotropic (LAI) strains promotes IL-4-induced IgE production, indicating that the HIV-1 infectious process may participate in the IgE production observed in vivo. The effect of membrane glycoproteins (gp160, gp120, and gp41) was also evaluated. It was found that gp120 specifically potentiates in a dose-dependent manner IL-4-induced IgE production and does not affect IL-4-induced IgG, IgA, or IgM production. In these experiments, gp160 was also found to upregulate IL-4-induced IgE production, whereas gp41 was ineffective. This effect of gp120, gp160, and HIV-1 infection on IgE synthesis was not observed in the absence of IL-4. In the presence of IL-4, the inducing effect of gp120 appeared to be indirect because gp120 did not modify purified B lymphocyte IgE production after IL-4 and anti-CD40 monoclonal antibody stimulation. As HIV-1 infection is associated with alterations of PBMC redox metabolism, the role of nitric oxide (NO) in this IgE production by human PBMCs was evaluated. In the presence of a specific inhibitor of NO synthase pathways (L-NAME), IgE production induced by IL-4 and gp120 was abolished. Taken together, these data indicate that HIV-1 envelope glycoprotein gp120 (and gp160) specifically enhances IL-4-induced IgE production by normal human PBMCs, probably through the regulation of the nitric oxide pathway.
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PMID:Role of nitric oxide in the promoting effect of HIV type 1 infection and of gp120 envelope glycoprotein on interleukin 4-induced IgE production by normal human mononuclear cells. 1071 Feb 13


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