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

Variations in cytokine production in patients with human immunodeficiency virus (HIV) infection could be involved in the physiopathology and in the progression of the disease. Therefore we studied the level of granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor alpha (TNF alpha) produced in patients with HIV infection at stage II (asymptomatic seropositives) and stage IV (AIDS) of the CDC classification, by using an enzyme amplified sensitivity immunoassay. We measured the level of GM-CSF and TNF alpha in supernatant of phytohemagglutinin-activated peripheral blood mononuclear cells from patients and healthy individuals. In one out of 10 stage II patients and 4 out of 14 stage IV patients, we obtained higher levels of GM-CSF than the mean + 2 S.D. of controls, but in 3 stage IV patients with very low CD4+ T lymphocyte counts (< 50/mm-3) compared to other patients, the GM-CSF values were very low. High levels of TNF alpha were detected in 3 out of 10 stage II and 6 out of 11 stage IV patients. The high values of TNF alpha were associated with high values of GM-CSF in stage II and in most of AIDS patients except those with very low CD4+ T cell counts, who produced low levels of GM-CSF. Plasma levels of cytokines were evaluated in 10 stage II, 22 stage IV patients and 20 controls. Increased levels of GM-CSF (more than 9 pg/ml) were observed in the plasma from 8 out of 10 stage II patients and 17 out of 22 stage IV patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Granulocyte-macrophage colony-stimulating factor and tumor necrosis factor alpha in patients with human immunodeficiency virus (HIV) type 1 infection. 790 21

Cytolytic T lymphocytes (CTLs) specific for the human immunodeficiency virus (HIV-1) envelope glycoproteins have been cloned from HIV-1-seronegative human volunteers immunized with HIV-1 gp160-based candidate vaccines. Although vaccine-induced CTLs can potentially contribute to the antiviral response by direct lysis of infected cells, these CTLs may also produce cytokines that alter HIV-1 gene expression in other infected cells present in the microenvironment where CTL-target cell interactions occur. Vaccine-induced CTL clones were therefore examined for production of cytokines that affect HIV-1 gene expression in chronically infected T lymphocytic and promonocytic cell lines. Enhancement of HIV-1 gene expression was observed with supernatants from CD4+ CTL clones and with supernatants from a subset of CD8+ CTL clones. For each clone studied, upregulation of HIV-1 gene expression in chronically infected T cell lines resulted from the antigen-specific release by CTLs of tumor necrosis factor alpha (TNF-alpha). CD4+ and CD8+ CTLs that released TNF-alpha on antigen stimulation were also shown to express a biologically active 26-kDa transmembrane form of TNF-alpha, which was sufficient to induce upregulation of HIV-1 gene expression in chronically infected T cells placed in direct contact with the CTLs. Supernatants from antigen-activated, vaccine-induced CD4+ and CD8+ CTLs also caused upregulation of HIV-1 gene expression in chronically infected promonocytic cells. A subset of CD8+ CTL clones also produced a soluble factor(s) that inhibited HIV-1 replication in acutely infected autologous CD4+ blasts. Supernatants from CD4+ CTLs had no effect on HIV-1 replication in acutely infected CD4+ blasts. These results suggest that cytokine production as well as cytolytic activity should be evaluated in the analysis of the potential antiviral effects of vaccine-induced CTLs.
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PMID:Cytokines from vaccine-induced HIV-1 specific cytotoxic T lymphocytes: effects on viral replication. 790 31

Peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus (HIV)-infected patients, asymptomatic or with acquired immunodeficiency virus, produced 10-fold less interleukin 12 (IL-12) free heavy chain and fivefold less biologically active IL-12 heterodimer than PBMC from uninfected healthy donors when challenged in vitro with the common human pathogen Staphylococcus aureus. In contrast, PBMC from HIV-infected individuals and uninfected control donors produced similar levels of tumor necrosis factor alpha, IL-1 beta, and IL-10, and PBMC from HIV-infected individuals produced three- to fourfold more IL-6 compared with PBMC from uninfected control donors. The defect in IL-12 production is not due to hyperproduction of IL-10, a cytokine exerting an autocrine-negative feedback on IL-12 production, but was directly related to HIV infection, as suggested by the reduced ability of monocytes infected in vitro with HIV to produce IL-12. IL-12 deficiency may be an important component of the immunodeficiency associated with HIV infection.
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PMID:Impaired interleukin 12 production in human immunodeficiency virus-infected patients. 790 24

J delta K cells were isolated as a chronically infected survivor cell line, following infection of Jurkat CD4+ T cells with dl-NF, a mutated strain of human immunodeficiency virus type 1 (HIV-1) containing a deletion of the long terminal repeat (LTR) NF-kappa B sites. J delta K cells exhibited very low levels of constitutive HIV production. HIV-1 expression was activated from J delta K cells by treatment with phorbol myristate acetate (PMA), sodium butyrate (NaB), or hexamethylene bisacetamide (HMBA), but not tumor necrosis factor alpha (TNF-alpha), confirming the role of NF-kappa B in mediating TNF-alpha induction of HIV transcription. The strong induction of HIV expression by NaB or HMBA in J delta K cells clearly demonstrates the existence of NF-kappa B-independent mechanisms of HIV activation in chronically infected cells. J delta K cells may provide a useful model for characterizing NF-kappa B-independent transcriptional activation of the HIV LTR.
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PMID:NF-kappa B-dependent and -independent pathways of HIV activation in a chronically infected T cell line. 791 75

The induction of immunoglobulin E (IgE) switching in B cells requires at least two signals. The first is given by either of the soluble lymphokines interleukin 4 (IL-4) or IL-13, whereas the second is contact dependent. It has been widely reported that a second signal can be provided by the CD40 ligand (CD40L) expressed on the surface of T cells, mast cells, and basophils. A defect in the CD40L has been shown recently to be responsible for the lack of IgE, IgA, and IgG, characteristic of the childhood X-linked immunodeficiency, hyper IgM syndrome (HIGM1). IgE can however be detected in the serum of some HIGM1 patients. In this study, we isolated T cell clones and lines using phytohemagglutinin (PHA) and allergen, respectively, from the peripheral blood of one such patient who expressed a truncated form of CD40L, and investigated their ability to induce IgE switching in highly purified, normal tonsillar B cells in vitro. Unexpectedly, 4 of 12 PHA clones tested induced contact-dependent IgE synthesis in the presence of exogenous IL-4. These clones were also shown to strongly upregulated IL-4-induced germline epsilon RNA and formed dense aggregates with B cells. Of the four helper clones, three were CD8+, of which two were characteristic of the T helper cell 2 (Th2) subtype. Two allergen-specific HIGM1 T cell lines, both of the Th0 subtype, could also drive IgE synthesis when prestimulated using specific allergen. All clones and lines were negative for surface expression of CD40L, and the mutated form of CD40L was confirmed for a representative clone by RNase protection assay and sequencing. The IgE helper activity could not be attributed to membrane tumor necrosis factor alpha (TNF-alpha) although it was strongly expressed on activated clones, and the addition of neutralizing anti-TNF-alpha antibody did not abrogate IgE synthesis. These results therefore suggest the involvement of T cell surface molecules other than CD40L in the induction of IgE synthesis, and that these molecules may also be implicated in other aspects of T-B cell interactions.
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PMID:T cell clones from an X-linked hyper-immunoglobulin (IgM) patient induce IgE synthesis in vitro despite expression of nonfunctional CD40 ligand. 796 60

Infection with a variant of simian immunodeficiency virus, SIVsmmPBj14, leads to severe acute disease in macaques. This study was designed to investigate the functional significance of previously described mutations in the viral long terminal repeat (LTR) and to elucidate their contribution to the unique phenotype of SIVsmmPBj14. LTR-directed transcription was measured by using luciferase reporter constructs that were transiently transfected into cultured cells. In a wide range of cell types, the basal transcriptional activity of the LTR from SIVsmmPBj14 was found to be 2- to 4.5-fold higher than that of an LTR from a non-acutely pathogenic strain. These LTRs differ by five point mutations and a 22-bp duplication in SIVsmmPBj14, which includes a nuclear factor kappa B (NF kappa B) site. Transcriptional differences between these LTRs were further enhanced by two- to threefold upon treatment of cells with phorbol ester or tumor necrosis factor alpha or by cotransfection with plasmids expressing NF kappa B subunits. Mutagenesis studies, and the use of a reporter construct containing an enhancerless promoter, indicate that these transcriptional effects are due principally to the 22-bp sequence duplication and the NF kappa B site contained within it. Finally, infectious virus stocks that were isogenic except for the LTR were generated. The LTR from SIVsmmPBj14 was found to confer an increase in the kinetics of virus replication in cultured cells. Inclusion of this LTR in recombinant SIVs also resulted in a two- to threefold rise in the extent of cellular proliferation that was induced in quiescent simian peripheral blood mononuclear cells. These studies are consistent with the hypothesis that LTR mutations assist SIVsmmPBj14 in responding efficiently to cellular stimulation and allow it to replicate to high titers during the acute phase of viral infection.
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PMID:Enhanced responsiveness to nuclear factor kappa B contributes to the unique phenotype of simian immunodeficiency virus variant SIVsmmPBj14. 796 69

We have examined the feasibility of using interferon (IFN) gene transfer as a novel approach to anti-human immunodeficiency virus type 1 (HIV-1) therapy in this study. To limit expression of a transduced HIV-1 long terminal repeat (LTR)-IFNA2 (the new approved nomenclature for IFN genes is used throughout this article) hybrid gene to the HIV-1-infected cells, HIV-1 LTR was modified. Deletion of the NF-kappa B elements of the HIV-1 LTR significantly inhibited Tat-mediated transactivation in T-cell lines, as well as in a monocyte line, U937. Replacement of the NF-kappa B elements in the HIV-1 LTR by a DNA fragment derived from the 5'-flanking region of IFN-stimulated gene 15 (ISG15), containing the IFN-stimulated response element, partially restored Tat-mediated activation of LTR in T cells as well as in monocytes. Insertion of this chimeric promoter (ISG15 LTR) upstream of the human IFNA2 gene directed high levels of IFN synthesis in Tat-expressing cells, while this promoter was not responsive to tumor necrosis factor alpha-mediated activation. ISG15-LTR-IFN hybrid gene inserted into the retrovirus vector was transduced into Jurkat and U937 cells. Selected transfected clones produced low levels of IFN A (IFNA) constitutively, and their abilities to express interleukin-2 and interleukin-2 receptor upon stimulation with phytohemagglutinin and phorbol myristate acetate were retained. Enhancement of IFNA synthesis observed upon HIV-1 infection resulted in significant inhibition of HIV-1 replication for a period of at least 30 days. Virus isolated from IFNA-producing cells was able to replicate in the U937 cells but did not replicate efficiently in U937 cells transduced with the IFNA gene. These results suggest that targeting IFN synthesis to HIV-1-infected cells is an attainable goal and that autocrine IFN synthesis results in a long-lasting and permanent suppression of HIV-1 replication.
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PMID:Inhibition of human immunodeficiency virus type 1 replication by a Tat-activated, transduced interferon gene: targeted expression to human immunodeficiency virus type 1-infected cells. 798 1

Ceramide, an intracellular lipid mediator of tumor necrosis factor alpha (TNF-alpha) action, was studied for its effects on the expression of the proviral human immunodeficiency virus type 1 genome in latently infected myelomonocytic cell lines U-1IIIB and OM-10.1. Ceramide treatment resulted in a 20- to 100-fold enhancement of HIV production in these cells. Ceramide also enhanced the expression of the chloramphenicol acetyltransferase gene directed by a human immunodeficiency virus type 1 long terminal repeat in transfected U-937 cells, indicating that ceramide acts at the level of viral transcription. These observations suggest that the TNF-ceramide signaling system may be involved in the regulation of HIV expression in certain myeloid cell types.
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PMID:Stimulation of human immunodeficiency virus type 1 expression by ceramide. 798 82

Human herpesvirus 6 variant A (HHV-6A) and human herpesvirus 6 variant B (HHV-6B) are closely related herpesviruses. No disease has been specifically associated with HHV-6A, whereas HHV-6B is the major etiologic agent of exanthem subitum. Both viruses may be opportunistic pathogens in the immunocompromised patient. HHV-6 genomes have low G+C contents for herpesviruses (43%); they consist of a 141-kb unique segment that is flanked by single copies of a directly repeated sequence that can vary from 10 to 13 kb. HHV-6A and HHV-6B encode homologs of many conserved herpesvirus proteins and are classified as beta-herpesviruses based on their close genetic relationship with human cytomegalovirus. HHV-6A and HHV-6B are even more closely related to the recently discovered human herpesvirus 7. HHV-6 encodes homologs of the seven genes that are essential for origin-dependent herpes simplex virus type 1 DNA replication, including the origin-binding protein, which has no clear homolog in human cytomegalovirus. The HHV-6B origin-binding protein binds to sequences with similarities to alpha-herpesvirus replication origins that lie within a genomic segment that can serve as a replication origin in transient replication assays. Both HHV-6 variants encode homologs of the adeno-associated virus type 2 Rep protein; the role of this protein during infection is unknown. HHV-6 induces synthesis of a broad range of host cell proteins, including interferon alpha, CD4, interleukin-1 beta, and tumor necrosis factor alpha, and also induces expression of the human immunodeficiency virus type 1 LTR promoter. Little is known about the process by which HHV-6 regulates gene expression.
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PMID:Molecular biology of human herpesviruses 6A and 6B. 801 36

Severe weight loss is a common manifestation of advanced infection with the human immunodeficiency virus. The level of tumor necrosis factor alpha (TNF-alpha), an inducer of cachexia in laboratory animals, is elevated in the serum of some patients with AIDS. In a pilot study, five patients with unexplained AIDS-related wasting were treated with pentoxifylline, a known suppressor of TNF-alpha production. Three of the five patients had elevated baseline serum levels of TNF-alpha, and these three patients did not have significant weight gain after 4-8 weeks of pentoxifylline therapy despite the reduction of serum TNF-alpha levels. The remaining two patients, who did not have elevated serum levels of TNF-alpha, continued to lose weight and developed extensive bacterial pneumonia within 3 weeks of starting pentoxifylline therapy. Thus, therapy with pentoxifylline did not clearly benefit the patients with AIDS-related wasting in this uncontrolled pilot study; indeed, it might have been harmful for a subgroup of these patients.
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PMID:Use of pentoxifylline therapy for patients with AIDS-related wasting: pilot study. 764 5


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