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

Previous studies have shown that HIV-1 exploits dendritic cells (DCs) to replicate and spread among CD4+ T cells. The DCs within mucosal surfaces may be especially important, but these are more difficult to access. To study more extensively the properties of DCs and other leukocytes from skin and different mucosae, DCs were isolated from uninfected macaques and their sensitivity assessed to infection with SIV in vitro. Dendritic cells and T cells readily emigrated from organ cultures of macaque skin, as described previously for humans. In addition, characteristic cells emigrated from explants of mucosae, both nasopharyngeal (adenoid and tonsil) and genital (vagina and cervix). The macaque DCs reacted with the monoclonals that are used to study human DCs, such as MAbs to CD40, CD86, CD83, and the p55 protein. When SIV was added to the DC-T cell mixtures from these different organs, extensive replication was observed in all but the cervical leukocytes. SIV replication occurred without the use mitogens, and with virus that had been grown in a cell line in the absence of mitogens and IL-2. Most of the newly synthesized viral protein is observed in syncytia. Therefore, mixtures of DCs and T cells isolated from mucosal surfaces served as a naturally permissive environment for SIV replication.
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PMID:Dendrite cell-T cell mixtures, isolated from the skin and mucosae of macaques, support the replication of SIV. 919 76

Early in HIV-1 infection, B cell responses to T cell-dependent antigens are impaired. In addition to the receptor-ligand pair CD40/CD40L, CD27/CD70 also appears to be involved in T cell-dependent B cell stimulation. We have shown that CD70+ B cells are the main producers of Ig when stimulated in a T cell-dependent manner, and that CD70 upregulation is dependent on interaction of CD40L on T cells with CD40 on B cells. We confirm here that B cells from HIV-infected individuals are impaired in T cell-dependent Ig production in vitro. This dysfunction could partly be restored by adding allogeneic T cells to the culture. In contrast, IgG production induced by CD40 MAb, IgM MAb, and IL-10 was in the normal range. In line with this, CD70 upregulation on B cells from HIV-infected individuals was impaired after stimulation in vitro by activated T cells but not after stimulation with CD40 MAb and IgM MAb. Furthermore, CD40L expression was decreased on CD4+ T cells after stimulation in vitro. Finally, CD70 expression on freshly isolated B cells from HIV-infected individuals was decreased, and low CD70 expression correlated with low IgG production after T cell-dependent stimulation. In conclusion, our data strongly suggest that impaired B cell responses to T cell-dependent Ag in HIV-1 infection are due to a defect in T cells.
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PMID:Functional B cell abnormalities in HIV type 1 infection: role of CD40L and CD70. 926 89

Human immunodeficiency virus (HIV)-1 infection is associated with the development of aggressive extranodal B-cell non-Hodgkin's lymphomas. Using microvascular endothelial cell (MVEC)-enriched bone marrow stromal cultures, HIV infection of stromal MVECs from lymphoma patients induced the outgrowth of malignant B cells. MVECs were the only HIV-infected cells in the stroma, and purified brain MVECs also induced a phenotype supportive of neoplastic B-cell attachment and proliferation. HIV infection of MVECs stimulated surface expression of CD40 and allowed preferential induction of the vascular cell adhesion molecule VCAM-1 after CD40 triggering. B-lymphoma cells expressed the CD40 ligand (CD40L), and blocking of CD40-CD40L interactions between HIV-infected MVECs and B-lymphoma cells inhibited B-cell attachment and proliferation. These observations suggest that HIV promotes B-lymphoma cell growth through facilitating attachment of lymphoma cells to HIV-infected MVECs and represent a novel mechanism through which viruses may induce malignancies.
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PMID:HIV-1 induction of CD40 on endothelial cells promotes the outgrowth of AIDS-associated B-cell lymphomas. 935 99

Dendritic cells (DC) are potent APC that may be involved in the pathogenesis of HIV-1 infection. We studied the APC function of DC from HIV-1-infected subjects that were derived from monocyte-depleted PBMC by culture in human IL-4 and human granulocyte-macrophage CSF. The cultured cells from the HIV-1-infected subjects had similar morphology and phenotype of mature DC (CD80 = 41 +/- 8%, CD86 = 77 +/- 5%, CD40 = 87 +/- 6%, CD1a = 1 +/- 1%) to DC cultured from seronegative subjects. The yield of these DC was lower than from HIV-1-seronegative subjects (4 +/- 0% vs 11 +/- 2%, p < 0.01), and the lower DC yields correlated with lower numbers of blood CD4+ T cells (r = 0.60, p < 0.01) and higher plasma viral load (r = -0.49, p < 0.01). DC from HIV-1-infected subjects were infected with recombinant vaccinia virus vectors expressing Gag, Pol, and Env and were able to stimulate equal or higher levels of MHC class I-restricted, anti-HIV-1 memory CTL (CTLm) than were similarly treated, autologous B lymphocyte cell lines. DC pulsed with peptides representing HIV-1 CTL epitopes stimulated higher levels of anti-HIV-1 CTLm responses than did DC infected with the vaccinia virus-HIV-1 constructs. Allogeneic, MHC class I-matched DC also stimulated anti-HIV-1 CTLm activity in cells from HIV-1-infected subjects. DC from early and late stages of HIV-1 infection had a similar ability to activate CTLm specific for targets expressing either HIV-1 genes via vaccinia virus vectors or HIV-1 immunodominant synthetic peptides. However, DC from either early or late stages of HIV-1 infection could not overcome the defect in anti-HIV-1 CTLm response in advanced infection.
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PMID:Cultured blood dendritic cells retain HIV-1 antigen-presenting capacity for memory CTL during progressive HIV-1 infection. 936 24

Monocyte-derived cultured dendritic cells (DCs) are potent antigen-presenting cells (APCs) and are susceptible to HIV-1Lai infection. Compared to the low level of virus production by HIV-1-infected DCs alone, a level of virus two to three orders of magnitude higher was produced by cocultivation of HIV-1-infected DCs with autologous resting CD4+ T cells in the presence of a nominal antigen. In this coculture system, direct contact of HIV-1-infected DCs with T cells was crucial for efficient virus transmission and subsequent virus production. Blocking of the LFA-1/ICAM-1 or LFA-3/CD2 interaction between these cells substantially reduced virus production, without influence or IL-2 production by activated T cells. In contrast, cell-cell transmission of HIV between non-APCs and activated T cells was not blocked by an antibody against LFA-3. Since a low level of virus production by HIV-infected DCs was upregulated by cross-linking of CD40, it was suggested that not only focal adhesion, but also mutual activation of HIV-infected DCs and T cells through adhesion molecules, may potentiate virus transmission and production and that such activation signals to HIV may be distinct from signals responsible for IL-2 production in activated T cells.
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PMID:Efficient virus transmission from dendritic cells to CD4+ T cells in response to antigen depends on close contact through adhesion molecules. 943 17

IL-12 production in HIV-infected (HIV+) individuals is severely impaired after stimulation by bacterial products or T cell-dependent stimuli. Because CD40-CD40 ligand (CD40L) interactions are the major mechanism involved in the T cell-dependent activation of antigen-presenting cells, we investigated whether this pathway was functional in HIV+ donors. CD40 expression was increased on freshly isolated monocytes from HIV+ individuals compared to HIV donors. However, equivalent CD40 expression was obtained in the two groups after cytokine stimulation. Since CD40 expression was intact in HIV+ donors' cells, we determined whether IL-12 production could be restored by providing exogenous T cell-dependent stimuli, CD40L and IFN-gamma, at the time of bacterial stimulation. IL-12 production was not altered by CD40L alone, was increased by IFN-gamma, and was synergistically restored to normal values by IFN-gamma + CD40L. This combination was more efficient for enhancing IL-12 production than granulocyte-macrophage colony-stimulating factor + CD40L or neutralizing anti-IL-10 antibody + CD40L. CD40L did not affect IL-10 production, whereas IFN-gamma significantly decreased it. This study demonstrates that the defect in IL-12 production by leukocytes from HIV+ donors can be overcome in vitro if the interacting cells are provided with the right T cell-dependent co-stimuli.
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PMID:CD40 ligand and IFN-gamma synergistically restore IL-12 production in HIV-infected patients. 952 Oct 75

Dendritic cells (DCs), which are the most potent antigen-presenting cells for T lymphocytes, are targets for HIV in vitro and in vivo. Antigen presentation by DCs has been suggested to be impaired during HIV infection; however, the extent to which DCs from HIV+ individuals are altered, particularly in lymphoid organs where T cell stimulation takes place, is not clear. To address this question, the levels of expression of functionally important molecules by spleen DCs from HIV+ patients (n = 6), and HIV- organ donors (n = 5) were compared. By rare event analysis of flow cytometry data, spleen DCs from HIV+ patients were not depleted, representing 0.6 +/- 0.4% of spleen mononuclear cells compared with 0.8 +/- 0.5% in HIV- spleens. Fresh HIV+ spleen DCs were MHC II+ and weakly CD86+CD40+, but negative for CD83 and CD80, and hence had a normal phenotype, showing no signs of in vivo activation. After 24 hr of culture, they upregulated the expression of MHC II, CD40, CD80, and CD86 to levels just as high as those on DCs from organ transplant donors. However, cultured DCs from HIV+ spleens showed lower expression of CD83, compared with DCs from HIV- spleens. The biological significance of this observation will be appreciated further when the function of this molecule is better known. These results suggest that putative defects in antigen presentation by DCs from HIV+ patients are not related to the surface expression of MHC II, CD40, CD80, or CD86.
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PMID:Low CD83, but normal MHC class II and costimulatory molecule expression, on spleen dendritic cells from HIV+ patients. 956 53

The mechanisms leading to polyclonal hypergammaglobulinemia in patients with human immunodeficiency virus (HIV) infection are not well understood. In light of the important role of interleukin-10 (IL-10) and the interaction between CD40 and CD40 ligand in the normal regulation of B-lymphocyte function and Ig production, we examined these parameters in 24 HIV-infected patients. Both plasma IL-10 levels and the percentage of CD4(+) and CD8(+) lymphocytes expressing CD40 ligand were significantly higher in the patients than in the 10 blood donor controls. Serum IgG correlated positively with circulating IL-10 levels and the percentage of CD4(+) lymphocytes expressing CD40 ligand. Furthermore, a single bolus infusion of intravenous Ig (0.4 g/kg) in 8 HIV-infected patients caused a further increase in IL-10 levels in plasma and an increase in both IL-10 and IgG production in peripheral blood mononuclear cell cultures. In another patient group (Wegener's granulomatosis) receiving a single bolus infusion of intravenous Ig, a similar increase in plasma IL-10 levels was found, suggesting that this may be a general effect of intravenous Ig. In patients with HIV infection, our data suggest that a vicious cycle may be operative where high endogenous Ig levels may enhance IL-10 production that, in turn, leads to higher Ig production.
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PMID:Possible role of interleukin-10 (IL-10) and CD40 ligand expression in the pathogenesis of hypergammaglobulinemia in human immunodeficiency virus infection: modulation of IL-10 and Ig production after intravenous Ig infusion. 980 66

Recently it has been shown that dendritic cells (DC) can develop from peripheral blood monocytes when grown in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). However, it is unclear whether DC can also develop from monocytes in absence of these cytokines. We therefore analyzed the effect of Flt-3 ligand (Flt3L) and of CD40 ligand on the development of human DC from blood monocytes in the absence of GM-CSF. Adherent peripheral blood mononuclear cells (PBMNC) were cultured in the presence of different cytokine combinations and analyzed for the expression of surface molecules and antigen presenting capacity. For functional analyses, cells were tested for their ability to stimulate allogeneic T lymphocytes in a mixed lymphocyte reaction (MLR), to present soluble antigens, and to induce primary HIV-peptide-specific cytotoxic T-cell (CTL) responses in vitro. Furthermore, expression of DC-CK1, a recently identified chemokine with specific expression in DC, and of IL-18 (IGIF), a growth and differentiation factor for Th 1 lymphocytes, was analyzed by reverse-transcription polymerase chain reaction (RT-PCR). In our study, Flt3L alone was not sufficient to generate DC and required addition of IL-4. DC generated with Flt3L and IL-4 underwent maturation after stimulation with tumor necrosis factor- (TNF-) or CD40L, characterized by CD83 expression, upregulation of MHC, adhesion, and costimulatory molecules as well as increased allogeneic proliferative response. In contrast, CD40 ligation alone promoted differentiation of adherent blood monocytes into functional DC in the absence of GM-CSF and IL-4. These cells displayed all phenotypic and functional characteristics of mature DC and were potent stimulatory cells in priming of major histocompatibility complex (MHC) class I-restricted CTL responses against an HIV-peptide, whereas their ability to present soluble protein antigens was reduced. Using a semiquantitative RT-PCR, DC-CK1 and IL-18 transcripts were detected in all generated DC populations, independent of growth factors used. Our findings provide further evidence for the importance of CD40-CD40L interaction for initiation and maintenance of T-cell responses and confirm the emerging concept that blood monocytes provide an additional source of DC depending on external stimuli.
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PMID:Generation of functional human dendritic cells from adherent peripheral blood monocytes by CD40 ligation in the absence of granulocyte-macrophage colony-stimulating factor. 983 29

Human immunodeficiency virus-associated Hodgkin's disease (HIV-HD) displays several peculiarities when compared with HD of the general population. These include overrepresentation of clinically aggressive histologic types and frequent infection of Reed-Sternberg (RS) cells by Epstein-Barr virus (EBV). Recently, we have reported that the histogenesis of HD of the general population may be assessed by monitoring the expression pattern of BCL-6, a transcription factor expressed in germinal center (GC) B cells, and of CD138/syndecan-1 (syn-1), a proteoglycan associated with post-GC, terminal B-cell differentiation. In this study, we have applied these two markers to the study of HIV-HD histogenesis and correlated their expression status to the virologic features of this disease. We have found that RS cells of all histologic categories of HIV-HD consistently display the BCL-6(-)/syn-1(+) phenotype and thus reflect post-GC B cells. Although BCL-6(-)/syn-1(+) RS cells of HIV-HD express CD40, they are not surrounded by CD40 ligand-positive (CD40L+) reactive T lymphocytes, which, in HD of the general population, are thought to regulate the disease phenotype through CD40/CD40L interactions. Conversely, RS cells of virtually all HIV-HD express the EBV-encoded latent membrane protein 1 (LMP1), which, being functionally homologous to CD40, may contribute, at least in part, to the modulation of the HIV-HD phenotype.
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PMID:Human immunodeficiency virus-associated Hodgkin's disease derives from post-germinal center B cells. 1009 Sep 42


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