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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human immunodeficiency virus (HIV) infection is associated with abnormalities of both T-cell and B-cell immunity in patients with acquired immunodeficiency syndrome (AIDS). Previous studies demonstrated deficient production of the cytokines interleukin-1 (IL-1), interleukin-2 (IL-2), and gamma interferon (IFN-gamma). Tumor necrosis factor alpha and tumor necrosis factor beta have not been previously investigated in AIDS. In this study we demonstrate that peripheral blood mononuclear cells from patients with HIV infection who have either AIDS-related complex or acquired immunodeficiency syndrome are deficient in the production of tumor necrosis factor alpha and tumor necrosis factor beta. These cytokines, derived predominantly from monocytes or lymphocytes, respectively, function as immunoregulatory, antitumor, and antiinfective proteins. A deficiency in their production may therefore be responsible for many of the complications associated with HIV infection in patients with AIDS-related complex or acquired immunodeficiency syndrome.
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PMID:Tumor necrosis factors alpha and beta in acquired immunodeficiency syndrome (AIDS) and aids-related complex. 369 21

In this study, we demonstrated that the protozoan parasite Leishmania donovani and one of its major surface molecules, the lipophosphoglycan (LPG), can induce human immunodeficiency virus type 1 (HIV-1) expression in U1 and OM-10.1, two cell lines of monocytoid origin latently infected with HIV-1. Treatment of U1 cells with various concentrations of LPG (1, 5, and 10 microM) resulted in a dose-dependent secretion of tumor necrosis factor alpha (TNF-alpha). Suppression of LPG-induced HIV-1 expression by polyclonal anti-TNF-alpha antibodies further confirmed the involvement of this cytokine. Results from these studies indicate that the protozoan parasite L. donovani can induce the secretion of TNF-alpha that will function in an autocrine or paracrine manner to upregulate HIV-1 expression. Our data suggest for the first time that this protozoan parasite can be viewed as a potential cofactor in the pathogenesis of AIDS.
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PMID:Activation of human immunodeficiency virus type 1 in monocytoid cells by the protozoan parasite Leishmania donovani. 747 54

The virus-encoded Tat protein strongly activates transcription of human immunodeficiency virus (HIV). A well-recognized mechanism involves interaction of Tat with the nascent RNA transcript of the viral tar gene; mutation of tar greatly decreases activation by Tat. However, Tat still provides a low level of activation, demonstrating that it also has a tar-independent mode of action. We propose that this tar-independent mode of Tat action is through activation of gene transcription to produce tumor necrosis factor alpha. This cytokine and other compounds that activate NF-kappa B up-regulate the HIV promoter at a low level, similarly to the second Tat action. Through this mechanism, they also activate promoters of tumor necrosis factor alpha and other cytokines and thereby establish an auto-up-regulatory loop. Activated NF-kappa B motifs in the HIV promoter synergize with Tat/tar. Mutations of these motifs decrease activation by Tat to a few percent of the wild-type value. In cooperation, the two modes of activation by Tat (tar dependent and cytokine based) set up positive up-regulatory loops which greatly superactivate transcription of HIV. Agents that block these synergistic pathways at three different steps and are more inhibitory in combination than is any one alone have been found. Thereby, multidrug modalities for transcription of HIV are proposed for virus suppression.
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PMID:A Tat-induced auto-up-regulatory loop for superactivation of the human immunodeficiency virus type 1 promoter. 749 49

Elevation of serum interleukin-1 beta (IL-1 beta) levels, and to a lesser degree tumor necrosis factor alpha levels, was found in cachectic human immunodeficiency virus (HIV)-infected African patients without concurrent opportunistic infection or neoplasia (HIV wasting syndrome). A heterogeneous pattern of elevations of cytokine levels, including mild elevations of IL-1 beta and pronounced elevations of IL-6 levels, was found in other cachectic states.
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PMID:Differential elevation of circulating interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6 in AIDS-associated cachectic states. 749 13

In the present study we have observed that interleukin (IL) 1 alpha or IL-1 beta directly induced expression of human immunodeficiency virus (HIV) in the latently infected human promonocytic cell line U1. In addition, IL-1 synergized with IL-6, but not with tumor necrosis factor, in the upregulation of virus expression in U1 cells as measured by accumulation of steady-state mRNAs and production of reverse transcriptase activity. The HIV inductive effect of IL-1 was blocked by transforming growth factor beta, anti-IL-1 antibodies, or monoclonal antibodies directed to the type 1, but not to the type 2, cell surface receptor for IL-1; the latter actually caused enhancement of the IL-1-mediated effect. Unlike tumor necrosis factor alpha, IL-1 either alone or in combination with IL-6 did not induce activation of the transcription activating factor NF-kappa B above the constitutive levels of unstimulated U1 cells. Finally, the IL-1 receptor antagonist effectively blocked IL-1-mediated direct and synergistic inductive effects on virus production. Thus, IL-1 may be an important mediator of HIV expression, and blocking of IL-1 expression and/or its effects may have a potential therapeutic role in the inhibition of HIV expression in infected individuals.
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PMID:Interleukin 1 induces expression of the human immunodeficiency virus alone and in synergy with interleukin 6 in chronically infected U1 cells: inhibition of inductive effects by the interleukin 1 receptor antagonist. 750 10

Recent information has suggested that posttranscriptional mechanisms, whereby human immunodeficiency virus type 1 (HIV-1) RNA exists as multiply spliced transcripts without promoting an accumulation of the larger messages, are responsible for maintaining a stable state of nonproductive viral expression or viral latency. To test the universality of these observations, we compared the patterns of viral RNA splicing and the frequencies of cells actually harboring HIV-1 RNA in four chronically HIV-1-infected cell lines (U1 [promonocytic], ACH-2 [T lymphocytic], OM-10.1 [promyelocytic], and J1.1 [T lymphocytic]). In uninduced U1 and ACH-2 cultures, a high frequency of cells (approximately one in six) contained HIV-1 RNA but mainly as multiply spliced transcripts, again supporting a posttranscriptional mechanism maintaining viral latency. In sharp contrast, only 1 in 50 cells in uninduced OM-10.1 and J1.1 cultures contained HIV-1 RNA, indicating a primary transcriptional mechanism controlling viral expression in these cells. Furthermore, those OM-10.1 and J1.1 cells that did contain viral RNA were in a state of productive HIV-1 expression marked by the presence of both spliced and unspliced transcripts. Even though the total absence of viral RNA in the majority of OM-10.1 and J1.1 cells indicated a state of absolute latency, treatment with tumor necrosis factor alpha induced transcription of HIV-1 RNA in nearly 100% of the cells in all four of the chronically infected cultures. Tumor necrosis factor alpha induction of U1, ACH-2, and OM-10.1 cultures resulted in an initial accumulation of multiply spliced HIV-1 RNA followed by a transition to the larger unspliced viral RNA transcripts. This RNA splice transition was less apparent in the J1.1 cell line. These results demonstrate that host cell-specific transcriptional and posttranscriptional mechanisms are important factors in the control of HIV-1 latency.
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PMID:Human immunodeficiency virus type 1 RNA expression by four chronically infected cell lines indicates multiple mechanisms of latency. 751 Nov 77

Studies presented here show that altering the intracellular redox balance by decreasing glutathione levels profoundly affects early signal transduction events in human T cells. In a T-cell receptor (TCR) signaling model, short-term pretreatment with buthionine sulfoximine, which specifically decreases intracellular glutathione, essentially abrogates the stimulation of calcium influx by anti-CD3 antibodies without significantly impairing other aspects of TCR-initiated signal transduction, such as overall levels of TCR-stimulated tyrosine phosphorylation. In an inflammatory-cytokine signaling model, the failure of tumor necrosis factor alpha to stimulate more than minimal tyrosine phosphorylation in lymphocytes is overcome by buthionine sulfoximine pretreatment--i.e., tumor necrosis factor alpha stimulates extensive tyrosine phosphorylation in glutathione-depleted lymphocytes. These redox-dependent changes in T-cell responsiveness suggest that the glutathione deficiency that we and others have demonstrated in human immunodeficiency virus-infected individuals may contribute significantly to the immunodeficiency and the increased inflammatory reactions in these individuals.
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PMID:Redox regulation of signal transduction: tyrosine phosphorylation and calcium influx. 751 25

Impaired polymorphonuclear neutrophil (PMN) function may contribute to the onset of certain life-threatening bacterial and fungal infections in human immunodeficiency virus (HIV)-infected patients. Published data on PMN functional activity in HIV infection are controversial, possibly because most studies have involved PMNs isolated from their blood environment by means of various procedures that may differently affect surface receptor expression and thereby alter cellular responses. We therefore used flow cytometry to study the expression of adhesion molecules at the PMN surface, actin polymerization, and the oxidative burst of whole-blood polymorphonuclear neutrophils in 42 HIV-infected patients at different stages of the disease. These PMNs were activated in vivo, as demonstrated by increased expression of the adhesion molecule CD11b/CD18, reduced L-selectin antigen expression, increased actin polymerization, and increased H2O2 production. The alterations were present in asymptomatic patients with CD4+ cell counts greater than 500/microL and did not increase with the progression of the disease. Stimulation by bacterial N-formyl peptides showed dysregulation of L-selectin shedding and decreased H2O2 production after ex vivo priming with tumor necrosis factor alpha or interleukin-8 (IL-8). These latter impairments, which correlated with the decrease in CD4+ lymphocyte numbers and with IL-8 and IL-6 plasma levels, could contribute to the increased susceptibility of HIV-infected patients to bacterial infections.
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PMID:Polymorphonuclear neutrophils from human immunodeficiency virus-infected patients show enhanced activation, diminished fMLP-induced L-selectin shedding, and an impaired oxidative burst after cytokine priming. 752 41

Mononuclear phagocytes (monocytes, macrophages, and dendritic cells) play major roles in human immunodeficiency virus (HIV) persistence and disease pathogenesis. Macrophage antigen presentation and effector cell functions are impaired by HIV-1 infection. Abnormalities of macrophage effector cell function in bone marrow, lung, and brain likely result as a direct consequence of cellular activation and HIV replication. To further elucidate the extent of macrophage dysfunction in HIV-1 disease, a critical activation-specific regulatory molecule, nitric oxide (NO.), which may contribute to diverse pathology, was studied. Little, if any, NO. is produced by uninfected human monocytes. In contrast, infection with HIV-1 increases NO. production to modest, but significant levels (2-5 microM). Monocyte activation (with lipopolysaccharide, tumor necrosis factor alpha, or through interactions with astroglial cells) further enhances NO. production in HIV-infected cells, whereas its levels are diminished by interleukin 4. These results suggest a possible role for NO. in HIV-associated pathology where virus-infected macrophages are found. In support of this hypothesis, RNA encoding the inducible NO synthase (iNOS) was detected in postmortem brain tissue from one pediatric AIDS patient with advanced HIV encephalitis. Corresponding iNOS mRNA was not detected in brain tissue from five AIDS patients who died with less significant brain disease. These results demonstrate that HIV-1 can influence the expression of NOS in both cultured human monocytes and brain tissue. This newly described feature of HIV-macrophage interactions suggests previously unappreciated mechanisms of tissue pathology that result from productive viral replication.
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PMID:Regulation of nitric oxide synthase activity in human immunodeficiency virus type 1 (HIV-1)-infected monocytes: implications for HIV-associated neurological disease. 753 Jul 62

The blood-brain barrier (BBB) functions to regulate the entry of macromolecules, microbial pathogens, and circulating leukocytes into the central nervous system (CNS). It consists, in part, of the microvascular endothelium and associated astrocyte foot processes, found in close apposition to the abluminal side of the vascular endothelial cells (EC). During the pathogenesis of certain nervous system diseases with inflammatory components, the BBB may function to facilitate the entry of leukocytes into the CNS parenchyma. A common histologic observation in human immunodeficiency virus type-1 (HIV) encephalitis is the localization of HIV proteins to multinucleated giant cells that co-immunolabel with antibodies specific for cells of the monocyte/macrophage lineage, suggesting that HIV can enter the CNS as cell-associated virus. We previously characterized a tissue culture model of the BBB that consists of the co-culture of autologous EC and astrocytes. In this presentation, we used this model to examine the expression of adhesion molecules by both the EC and astrocyte components of this BBB model, and to characterize the interactions between HIV-infected monocytes and EC. The data presented in this review of our work demonstrates that astrocytes upregulate the expression of intercellular adhesion molecule (ICAM-1) by EC. In a parallel study, western blot analysis demonstrated that ICAM-1 is also expressed in the developing human CNS. When exposed to the proinflammatory cytokine tumor necrosis factor alpha (TNF), both EC cocultured with astrocytes and astrocytes cultured alone expressed the adhesion proteins IG9, ICAM-1, vascular cell adhesion molecule 1 (VCAM) and E-selection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of the blood-brain barrier in HIV infection of the central nervous system. 753 41


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