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

There is substantial evidence that dendritic cells (DC) residing within epithelial surfaces (e.g., Langerhans cells) are the initial cells infected with HIV after mucosal exposure to virus. To study DC-HIV interactions in detail, we propagated Langerhans cell-like DC from cord blood CD34(+) cells and from adult blood plastic-adherent PBMC in the presence of cytokines (GM-CSF, IL-4, and/or TNF-alpha). DC pulsed overnight with HIVBaL or HIVIIIB were infected productively with both viral subtypes (as assessed by PCR, supernatant p24 protein levels, electron microscopy, and antibody staining). Productive infection could be blocked by anti-CD4 mAbs, RANTES (regulated upon activation, normal T cell expressed and secreted) (for HIVBaL), stromal cell-derived factor-1 (for HIVIIIB), or azidothymidine added during the HIV pulse, as well as by blocking DC proliferation. However, pulsing DC with HIV under these blocking conditions had no effect on the ability of DC to capture virus and transmit infection to cocultured antigen-stimulated CD4(+) T cells. Thus, we show by several criteria that (a) productive infection of DC and (b) the ability of DC to capture virus are mediated through separate pathways. We suggest that strategies designed to block mucosal transmission of HIV should consider interfering with both virus infection and virus capture by DC.
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PMID:Productive infection of dendritic cells by HIV-1 and their ability to capture virus are mediated through separate pathways. 932 69

DP IV/CD26 is involved in regulation of DNA synthesis and proliferation as well as production of cytokines of hematopoietic cells under various conditions. Inhibition of DNA synthesis in T lymphocytes, B lymphocytes, NK cells and myelomonocytic cells as well as of the production of IL-2, IL-6 TNF alpha, IL-1, IL-10, IL-12, IL-13, IFN-gamma, GM-CSF are not due to apoptosis of these cells. DP IV/CD26 inhibitors induce TGF-beta 1 mRNA synthesis and latent protein release demonstrating a crucial role of TGF-beta 1 in mediating CD26 function. X-X-Pro peptides as HIV-Tat protein strongly inhibit DP IV enzymatic activity and suppress DNA synthesis. This group of peptides may represent a class of natural DP IV/CD26 ligands and effectors, respectively. Hyperphosphorylation of p56lck as well as protein tyrosine phosphorylation of a number of proteins in T lymphocytes can be modulated by DP IV inhibitors. These data suggest that enzymatic activity or, at least in part, the active site of DP IV are both essential for its regulatory function in lymphocytes. Further work is required to determine the natural ligands, i.e. substrates and effectors, which are play the central role in DP IV/CD26 action in T cell growth and to understand the molecular mechanism of the early steps of this fundamental process.
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PMID:CD26/dipeptidyl peptidase IV in lymphocyte growth regulation. 933 Jun 89

To further clarify the complex transcriptional regulation of the human GM-CSF gene, which was extensively investigated in activated T cells, we have studied the role of an upstream NF-kappaB like site in the 5637 non-lymphoid cell line, which derives from a bladder carcinoma and constitutively produces GM-CSF. This sequence, named the A element, has an active role on GM-CSF transcription and is responsive to the tumor promoter PMA in transient transfection experiments. We describe here a heterodimeric binding complex of NF-kappaB subunits (c-Rel and p65) which is identical to the one obtained using the HIV-LTR-kappaB site as recognition sequence and different from the one (c-Rel and p50) observed with nuclear extracts from Mo T-lymphoid HTLV-II infected cells.
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PMID:c-Rel and p65 subunits bind to an upstream NF-kappaB site in human granulocyte macrophage-colony stimulating factor promoter involved in phorbol ester response in 5637 cells. 941 29

Monocyte-macrophages can be productively infected by CCR5-specific, but not CXCR4-specific, HIV-1. This could be due either to the absence of this chemokine receptor in this cell lineage or to other, yet undefined cellular cofactors that modulate the coreceptor activity of the CXCR4 in these cells. To investigate the basis of macrophage tropism, we studied the expression of CCR5 and CXCR4, as well as several of the other CC chemokine receptors, on monocyte-macrophages at different stages of differentiation. We found that on fresh monocytes, CXCR4 was relatively abundant, but it fell to barely detectable levels in culture over 24 hr and maintained this low level of expression during differentiation in vitro. Some donor macrophages appeared to express CXCR4 at levels comparable to CCR5. In contrast, CCR5 expression was low on fresh monocytes but increased on in vitro differentiation. Taken together, the results show that monocyte-macrophage differentiation is associated with a differential expression of chemokine receptors that may contribute to, but does not fully account for, the selectivity of these cells to HIV entry. GM-CSF, a cytokine that induces macrophage differentiation, caused a rapid decrease in CXCR4 and CCR5 mRNA and was correlated with decreased ability to support HIV entry.
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PMID:Chemokine receptor regulation and HIV type 1 tropism in monocyte-macrophages. 946 23

beta-chemokines play an important role in the development of immunologic reactions. Macrophages are major beta-chemokine-producing cells during T-cell directed, delayed-type hypersensitivity reactions in tissues, and have been reported to be important producers of beta-chemokines in the lymph nodes of HIV-1-infected individuals. However, the physiological signals responsible for inducing macrophages to produce beta-chemokines have not been established. Two soluble T cell products, interferon-gamma and granulocyte-macrophage colony stimulating factor, were added to cultured macrophages, but failed to stimulate the production of macrophage inflammatory protein-1alpha and -1beta; regulated upon activation, normal T cell expressed and secreted (RANTES); or monocyte chemoattractant protein-1. Instead, direct cell-cell contact between macrophages and cells engineered to express CD40L (also known as CD154) resulted in the production of large amounts of macrophage inflammatory protein-1alpha and -1beta, and RANTES (all ligands for CCR5), and monocyte chemoattractant protein-1 (a ligand for CCR2). Supernatants from CD40L-stimulated macrophages protected CD4(+) T cells from infection by a nonsyncytium-inducing strain of HIV-1 (which uses CCR5 as a coreceptor). These results have implications for granulomatous diseases, and conditions such as atherosclerosis and multiple sclerosis, where CD40L-bearing cells have been found in the macrophage-rich lesions where beta-chemokines are being produced. Overall, these findings define a pathway linking the specific recognition of antigen by T cells to the production of beta-chemokines by macrophages. This pathway may play a role in anti-HIV-1 immunity and the development of immunologic reactions or lesions.
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PMID:CD40 ligand (CD154) stimulation of macrophages to produce HIV-1-suppressive beta-chemokines. 956 Feb 54

The expression of many cytokines is dysregulated in individuals infected with the human immunodeficiency virus-1 (HIV-1). To determine the effects of HIV-1 infection on cytokine expression in individual cells (at the single cell level), we investigated the intracellular levels of proinflammatory cytokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, IL-6, and IL-8) and hematopoietic growth factors (granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF]) in monocyte-derived macrophages, mock-infected, or infected with HIV-1 by immunocytochemical staining for cytokine protein and compared this with secreted cytokine levels as determined by specific enzyme-linked immunosorbent assay (ELISA). No difference in the frequency or intensity of cell-associated immunocytochemical cytokine staining could be observed between HIV-1 and mock-infected cells even though the level of secreted proinflammatory cytokines increased and the hematopoietic growth factors decreased in HIV-1-infected cultures. Furthermore, equal expression of cytokine mRNA was observed in all cells in the culture regardless of whether the cells were productively infected with HIV-1 as determined by double-labelling immunocytochemical staining for HIV-1 p24 antigen and in situ hybridization for cytokine mRNA expression. These results indicate that HIV-1 infection results in dysregulation of intracellular cytokine mRNA expression and cytokine secretion not only in HIV-1-infected cells, but also through an indirect way(s) affecting cells not producing virus.
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PMID:Individual cell analysis of the cytokine repertoire in human immunodeficiency virus-1-infected monocytes/macrophages by a combination of immunocytochemistry and in situ hybridization. 961 74

The present study demonstrates the susceptibility of astrocytes to infection with SIVmac251. Indeed, primary cultures of astrocytes derived from simian adult brains, can be infected in vitro with the SIVmac251. Results show that SIVmac251 establishes a persistent infection in primary astroglial cultures and that viral replication can be reactivated by TNF-alpha, GM-CSF, IFN-gamma. Viral proteins as Nef, Rev, Vpx and occasionally gp120/160 are evidenced by immunocytochemistry. In vivo SIVmac251 and/or HIV-2 infected astrocytes have been isolated from brains of macaques following ex vivo primary cultures. The whole of these results demonstrated that, in this model, SIV establishes a persistent state of infection of astrocytes, that viral replication can be reactivated by cytokines and moreover suggest strongly an in vivo infection of astrocytes in the brain of these infected macaques.
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PMID:[Astrocytes and lentivirus infection in an experimental models of macaque infected with SIVmac251]. 975 61

Marijuana, a widely abused drug in the US, and its derivatives (cannabinoids) have been used in AIDS and cancer patients for treatment of intractable nausea and cachexia. Yet, objective investigations of the effect of cannabinoids on the human immune system are few. We investigated the effect of delta9 tetrahydrocannabinol (THC) and cannabidiol (CBD) on cytokine production in vitro by human leukemic T, B, eosinophilic and CD8+ NK cell lines as models. THC decreased constitutive production of IL-8, MIP-1alpha, MIP-1beta, and RANTES and phorbol ester stimulated production of TNF-alpha, GM-CSF and IFN-gamma by NK cells. It inhibited MIP-1beta in HTLV-1 positive B-cells but tripled IL-8, MIP-1alpha and MIP-1beta in B-cells and MIP-1beta in eosinophilic cells but doubled IL-8. Both cannabinoids strongly inhibited IL-10 production by HUT-78 T-cells. Results indicate that THC and nonpsychotropic CBD have complex lineage and derivative specific effects on cytokines consistent with previous animal studies. These effects while of potential benefits in some inflammatory/autoimmune diseases may worsen HIV infection, tumorigenesis and allergic inflammation in the lung.
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PMID:Delta9 tetrahydrocannabinol and cannabidiol alter cytokine production by human immune cells. 985 61

We investigated whether culture conditions could affect the RANTES antiviral effect on human immunodeficiency virus type 1 (HIV-1) infection of primary macrophages. Monocyte-derived macrophages (MDM) were obtained either as (1) the adherent cells of 5-day cultures of blood mononuclear cells (PBMC), followed by 2 days without nonadherent PBMC or added cytokines (MDM-5d), or (2) as the adherent cells recovered from 1-h incubation of PBMC, which were cultured for 7 days with macrophage colony-stimulating factor (M-CSF; MDM-MCSF). Infection of MDM-5d from different donors with HIV-1 R5 strains was reproducibly inhibited by RANTES (IC50 < or = 10 nM), but infection of MDM-MCSF was not inhibited by > or = 100 nM RANTES, even when added at initiation of cultures, although it was still inhibited by a CD4 antibody. RANTES had no antiviral effect when MDM-5d were treated with physiological concentrations of M-CSF or GM-CSF before infection. CCR5 and CXCR4 expression as well as that of other cell surface molecules, including adhesion molecules, was not affected by the cytokines. MDM-MCSF from delta 32CCR5 homozygous individuals did not render them permissive to HIV-1, suggesting that it is unlikely that the virus uses another coreceptor. RANTES binding to MDM was chondroitin sulfate, but not heparan sulfate, dependent, and RANTES bound more efficiently to MDM-5d than to MDM-MCSF. Chondroitin sulfate removal partially offset the RANTES antiviral effect for MDM-5d. Thus RANTES anti-HIV-1 activity for primary macrophages depends on culture conditions and their consequent activation status, which may lead to differences in proteoglycan surface expression. These data may be relevant for the development of chemokine-based therapy for HIV-1 infection.
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PMID:The inhibitory effect of RANTES on the infection of primary macrophages by R5 human immunodeficiency virus type-1 depends on the macrophage activation state. 987 20

Vaccination with HIV-1 DNA sequences induce both humoral and cellular immune responses in experimental animals. However, these responses are relatively weak and are often only transient in their nature. In order to enhance the level of HIV-1 specific immunity, we have engineered HIV-1 DNA constructs which contained various cytokine genes such as interleukin-2 (IL-2), granulocyte-macrophage colony stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) gene. These constructs have deleted the tat and nmf genes of HIV-1 to eliminate their immunosuppressive effects. Immunizations with these recombinant constructs elicited moderate proliferative T cell responses but poor antibody responses in rats. However, inoculations of HIV-1 DNA that contained the GM-CSF or the IL-2 gene significantly enhanced humoral and proliferative T cell responses, respectively. Thus, recombinant HIV-1 genomes such as those described here may increase the efficacy of DNA vaccination.
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PMID:DNA inoculations with HIV-1 recombinant genomes that express cytokine genes enhance HIV-1 specific immune responses. 1007 26


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