Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) is a type II C-type lectin that functions as an adhesion receptor and mediates binding and internalization of pathogens such as virus (human immunodeficiency virus, hepatitis C), bacteria (Mycobacterium), fungi, and parasites. DC-SIGN expression in vivo is primarily restricted to interstitial dendritic cells (DC) and certain tissue macrophages. We now report that leukemic THP-1 cells, widely used as a model for monocyte-macrophage differentiation, express very low basal levels of DC-SIGN and that DC-SIGN expression in THP-1 cells is regulated during differentiation. Differentiation-inducing agents (phorbol ester, bryostatin) conveyed THP-1 cells with the ability to up-regulate DC-SIGN mRNA levels and cell surface expression in response to interleukin-4 (IL-4) or IL-13. DC-SIGN up-regulation required a functional JAK-STAT signaling pathway, was inhibited in the presence of lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF-alpha), and conferred THP-1 cells with increased pathogen recognition and T cell stimulatory capabilities. The up-regulation of DC-SIGN on THP-1 cells resembles its inducible expression on monocytes and macrophages, where DC-SIGN expression is also induced by IL-4/IL-13 and negatively regulated by TNF-alpha, LPS, and vitamin D(3). These results point to THP-1 cells as a useful cellular system to characterize the pathogen-binding capabilities of DC-SIGN and to dissect the molecular mechanisms that control its regulated and tissue-specific expression in myeloid dendritic cells, and the results suggest that DC-SIGN constitutes a marker for both DC and alternatively activated macrophages.
 ...
PMID:Regulated expression of the pathogen receptor dendritic cell-specific intercellular adhesion molecule 3 (ICAM-3)-grabbing nonintegrin in THP-1 human leukemic cells, monocytes, and macrophages. 1507 Sep 1

Myeloid dendritic cells (MyDCs), prime stimulators of antigen-specific immunity, can serve as one of the major reservoirs for human immunodeficiency virus type-1 (HIV-1). Utilizing mature monocyte-derived MyDCs generated with granulocyte/macrophage colony-stimulating factor, interleukin-4, and tumour necrosis factor-alpha as an in vitro model, we here present the first proof of concept for liposomal compound delivery to these cells by specifically addressing CD209, i.e. DC-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN), a MyDC-associated C-type lectin implicated in the transmission of HIV-1 to T helper cells. By employing a liposomally entrapped tracer, calcein, we demonstrate by flow cytometry and mathematics a superior targeting efficacy for DC-SIGN, as compared with select other MyDC markers (CD1a, CD4, CD45R0, and CD83). Fluorescence microscopy reveals time-dependent surface binding and intracellular uptake of DC-SIGN-specific liposomes by both immature and mature MyDCs. This pilot study implies that liposomal targeting to CD209 and related C-type lectins may afford therapeutic intracellular drug delivery to MyDCs and other reservoir and nonreservoir cells susceptible to infection with HIV-1.
 ...
PMID:DC-SIGN-specific liposomal targeting and selective intracellular compound delivery to human myeloid dendritic cells: implications for HIV disease. 1514 50

Recent findings suggest that macrophage-tropic human immunodeficiency virus type 1 (HIV-1) produced in colostrum/early breast milk may hold a clue to determine the mechanisms of transmission of HIV-1 via breast-feeding. Here, we show that the majority of CD4(+) cells in the colostrum are CD14(+) macrophages expressing both chemokine receptors and DC-SIGN, a dendritic cell-specific receptor for HIV-1. The R5-type macrophage-tropic HIV-1 isolate NL(AD8) infected such breast-milk macrophages and caused them to secrete virus particles efficiently; however, the secreted virions showed only a weak transmissibility to their susceptible target, MAGIC-5 cells. When stimulated with interleukin-4, the breast-milk macrophages demonstrated a striking enhancement of expression of DC-SIGN and showed a strong capacity to transmit NL(AD8) virions to MAGIC-5 cells, which was specifically blocked by anti-DC-SIGN-specific antibody. These results suggest that HIV-1 virions captured by DC-SIGN, but not secreted cell-free virions, may be more efficiently transmitted to other compartments, such as the gastrointestinal tract, through acidic gastric juice.
 ...
PMID:Transmission of macrophage-tropic HIV-1 by breast-milk macrophages via DC-SIGN. 1560 26

Interleukin-4 is implicated in the pathogenesis of HIV-induced AIDS and causes enhancement of replication of virus strains that use the CXCR4 (X4) coreceptor. In this study, we explored the effects of interleukin-4 (IL-4) antisense (AS) DNA on replication of X4, simian human immunodeficiency viruses, SHIV(KU-2) and SHIV89.6P. AS IL-4 oligomer caused inhibition of virus replication in cultures of CD4+ T cells and macrophages derived from macaques. Plasmid expressing AS IL-4 DNA was also effective in abrogating virus replication in macrophage cultures. Relevance of these cell culture studies was confirmed in vivo by treating SHIV89.6P-infected macaques with AS IL-4 DNA. Six macaques were inoculated with the virus, and 4 were treated with AS IL-4 DNA. This resulted in a significant decrease in viral RNA concentrations in the liver, lungs, and spleen tissues that are all sites of virus replication in macrophages. This is the first demonstration of effective inhibition of an HIV-like virus in tissues by AS DNA of a cytokine. In the present era of increasing resistance of HIV to antiviral compounds, exploration of adjunct therapies directed at host responses in combination with antiretroviral drugs may be of value for the treatment of AIDS.
 ...
PMID:Inhibition of pathogenic SHIV replication in macaques treated with antisense DNA of interleukin-4. 1561 69

We generated human dendritic cell (DC) hybridoma cell lines by fusing HGPRT-deficient promonocytic U937 cells with immature DCs obtained by culturing peripheral blood monocytes with interleukin-4 (IL-4; 1,000 U/ml) and granulocyte-macrophage colony-stimulating factor (100 U/ml) for 7 days and mature DCs by treatment with tumor necrosis factor alpha (12.5 microg/ml) for 3 days. Only one fusion with immature DCs was successful and yielded four cell lines--HB-1, HB-2, HB-3, and HB-9--with an overall fusion efficiency of 0.0015%. The cell lines were stable in long-term culture, displayed morphological features typical of DCs, and expressed distinct class I and class II molecules not present on U937 (A*031012, B*51011, Cw*0701, DRB3*01011 52, and DR5*01011). A representative cell line, HB-2, that expressed DC markers including CD83, CD80 and CD86 could be induced to produce IL-12 through CD40 stimulation. After human immunodeficiency virus (HIV) infection, there was impairment of antigen-presenting cell (APC) function, which was manifested by an inability to stimulate allogeneic T-cell responses. There was no change in expression of major histocompatibility complex class I and class II antigens, CD83, CD40, CD4, CD11c, CD80, CD86, CD54, and CD58, or IL-12 production in the HIV-infected HB-2 cells. The HIV-infected HB-2 cells induced T-cell apoptosis in the cocultures. T-cell proliferation could be partially restored by using ddI, indinivir, and blocking anti-gp120 and anti-IL-10 antibodies. Our data suggest that there are multiple mechanisms that DCs use to inhibit T-cell responses in HIV-infected patients. The HB-2 cell line could be a useful model system to study APC function in HIV-infected DCs.
 ...
PMID:Impaired accessory cell function in a human dendritic cell line after human immunodeficiency virus infection. 1575 59

Good's syndrome is a rare adult-onset immunodeficiency disease characterized by hypogammaglobulinemia and thymoma. A 61-year-old male patient was diagnosed with Good's syndrome after a 2-year history of recurrent respiratory infections. Chest X-ray and chest computed tomography scan showed a mediastinal mass which was surgically removed. Histology revealed a thymoma. Following surgery he presented with recurrent respiratory and urinary tract infections and with esophageal candidiasis, even though his overall conditions dramatically improved after starting treatment with an appropriate dosage of intravenous immunoglobulins. Laboratory tests showed hypogammaglobulinemia, mild neutropenia, lymphopenia with no B cells, decreased CD4+ lymphocytes with an inverted CD4/CD8 ratio and increased interleukin-4-producing CD4+ lymphocytes, suggestive of an excessive Th2 response.
 ...
PMID:[Hypogammaglobulinemia and thymoma (Good's syndrome): a case report and a literature review]. 1585 97

To gain insight into the role of dendritic cells (DCs) in feline immunodeficiency virus (FIV) infection and immunity, methods were developed to culture feline myeloid DCs from CD14(+) monocytes with a combination of human recombinant granulocyte-macrophage colony-stimulating factor (hrGM-CSF) and interleukin-4 (hrIL-4). These cells were compared with feline macrophages cultured in the presence of hrGM-CSF. As with DCs in other species, feline DCs showed uniformly high MHC class II expression, moderate B7.1 expression, potent induction of the allogeneic mixed leucocyte reaction (MLR), and moderate uptake of fluorescein isothiocyanate-dextran (FITC-DX) in the endocytic assay. In comparison with feline macrophages, DCs showed higher expression of MHC class II, similar expression of B7.1, CD14, CXCR4 and CD1a, and lower expression of CD11b. When placed on alcian blue-coated glass slides, DCs differed from macrophages in showing a greater tendency to spread out; they also had characteristic fine cytoplasmic processes instead of the broader pseudopodia of macrophages. Basal IL-12 mRNA expression and FITC-DX uptake were greater in DCs than in macrophages. Unlike feline DCs, feline macrophages exhibited a dose-dependent suppressive effect in the MLR. Feline DCs propagated in vitro should prove useful in the development of DC-mediated vaccination and therapy for infectious and neoplastic feline diseases. Additionally, macrophages cultured with GM-CSF provide a potential means of studying the mechanism of immunosuppression in cats.
 ...
PMID:Culture and comparison of feline myeloid dendritic cells vs macrophages. 1603 26

Dendritic cells (DCs) are professional antigen-presenting cells that can prime T cells and polarize the cellular immune response. Because Th1-type immune responses have been connected to success in combating viral infection, a promising therapeutic application of DCs would be their differentiation in vitro and injection back into the host to boost an immune response in infected animals. This study was aimed both at developing a protocol to cultivate feline DCs in the absence of exogenous proteins for their use in vivo and at investigating what might be the most appropriate stimulus to induce their maturation in vitro and finding correlates of maturation. We generated DCs from peripheral blood monocytes in the presence of feline interleukin-4 and granulocyte-macrophage colony stimulating factor, and after 5 days their maturation was induced with either lipopolysaccharide, human recombinant tumor necrosis factor alpha, poly(I:C), or activated feline platelets. After 48 h, their CD14, CD1a, major histocompatibility complex class II, and B7.1 surface expression was analyzed in parallel with their ability to uptake antigen or prime a mixed leukocyte reaction. The results presented show that feline DCs cultured in autologous plasma differentiate and are able to mature in the presence of stimuli similar to the ones currently used for other species. The present work sets the grounds for future use of DCs obtained by the protocol described for in vivo vaccination and immunotherapy of feline immunodeficiency virus-infected cats.
 ...
PMID:Generation of feline dendritic cells derived from peripheral blood monocytes for in vivo use. 1621 Apr 84

Human immunodeficiency virus (HIV)-related opportunistic infections continue to occur in patients who are newly diagnosed with HIV infection, those in the early course of highly active antiretroviral therapy or nonadherent to HIV care, and other immunosuppressed individuals. One of the most common opportunistic infections in these patients is Pneumocystis pneumonia. CD8+ T cells are recruited to the lung after P. carinii infection and have been associated with both lung injury and host defense. This variability may be due to subpopulations of CD8+ T cells recruited to the lung. We have previously shown using adoptive transfer studies that in vivo-generated T-cytotoxic-1 (Tc1) CD8+ T cells, defined by the secretion of gamma interferon (IFN-gamma), have effector activity against Pneumocystis spp. in vitro as well as in vivo. To better understand the mechanisms of these effects, we generated, expanded, and tested Tc1 and Tc2 CD8+ T cells specific for P. murina ex vivo. Tc1-polarized CD8+ T cells secreted higher levels of IFN-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF) and lower levels of interleukin-4 (IL-4), IL-5, IL-10, and IL-13 than Tc2 CD8+ T cells when stimulated with P. murina antigen. Moreover, Tc1 CD8+ T cells demonstrated enhanced effector activity in a macrophage-mediated killing assay which was independent of cell contact. The augmentation in macrophage-mediated P. murina killing was significantly abrogated when GM-CSF was neutralized in the Tc1 CD8+ T cells. These data support the possibility that antigen-specific GM-CSF secretion is critical for effector activity of P. murina-specific Tc1 CD8+ T cells in vitro.
 ...
PMID:In vitro effector activity of Pneumocystis murina-specific T-cytotoxic-1 CD8+ T cells: role of granulocyte-macrophage colony-stimulating factor. 1623 46

In the pathogenesis of feline immunodeficiency virus (FIV) infection, feline dendritic cells (feDCs) are thought to play an important role. As with DCs in other species, feDCs are believed to transport virus particles to lymph nodes and transfer them to lymphocytes. Our investigation has focused on the ability of feDCs to influence the infection of syngeneic peripheral blood mononuclear cells (PBMCs) and allogeneic thymocytes. feDCs were derived from bone marrow mononuclear cells that were cultured under the influence of feline interleukin-4 and feline granulocyte-macrophage colony-stimulating factor. By using these feDCs in co-culture with resting PBMCs, an upregulation of FIV replication was shown. An enhancement of FIV infection was also detected when co-cultures of feDCs/feline thymocytes were infected. To obtain this enhancement, direct contact of the cells in the co-culture was necessary; transwell cultures showed that the involvement of only soluble factors produced by feDCs in this process is not likely. These feDCs were also able to induce the proliferation of resting thymocytes, which might explain the enhanced FIV replication observed. Together, these data suggest that feDCs have abilities similar to those shown for simian and human DCs in the interaction with leukocytes. This system is suitable for further investigations of the interplay of DC and T cells during FIV infection in vitro.
 ...
PMID:Feline immunodeficiency virus infection is enhanced by feline bone marrow-derived dendritic cells. 1717 Apr 58


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>