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

We have studied the pattern of expression of the lymphokines tumor necrosis factor (TNF alpha) and lymphotoxin (TNF beta) in T-cell lines established by transformation with human T-lymphotropic virus, type I (HTLV-I), the etiologic agent of adult T-cell leukemia (ATL). We report here that nine of nine HTLV-I-infected T-cell lines, established by in vitro infection with HTLV-I, including those with CD4+ or CD8+ as well as CD4-/CD8- phenotypes, constitutively produce high levels of TNF alpha and -beta mRNA and secrete biologically active TNF beta into the culture medium. Similar patterns of expression are seen in six of six HTLV-I-infected T-cell lines directly established from ATL patients. In contrast, several T-cell lines, either uninfected or infected with human immunodeficiency virus I, did not produce comparable levels of the TNF beta. Comparisons of a normal functional T-cell clone before and after infection with HTLV-I show that expression of TNF beta mRNA is induced in the infected cells. The high level expression in HTLV-I-infected cell lines dose not seem to involve perturbation of the TNF alpha/beta genetic loci by proviral integration. A cell line (81-66/45) nonproductively transformed with HTLV-I that produces tat-1 in the absence of viral structural proteins, produces both TNF alpha and -beta mRNA. This suggests that expression of these cytokines could be mediated in trans by the tat-1 gene product.
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PMID:Human T-lymphotropic virus I-infected T cells constitutively express lymphotoxin in vitro. 278 72

Retroviral infections are accompanied by immunosuppression in a variety of species. For feline leukemia virus, the immunosuppression has been ascribed to the transmembrane envelope protein, p15E, which suppresses the proliferative responses of cat, mouse, and human lymphocytes. A similar suppressive effect has been shown for a lysate of human immunodeficiency virus (HIV), strain HTLV-IIIB. Here we determined that detergent-disrupted HTLV-IIIB lystate exerted a strong suppressive effect on PHA-stimulated lymphocytes. Preparations of whole virions, a lysate of a local HIV isolate grown on MP-6 cells, and a commercially obtained UV and psoralene-inactivated lysate were examined and demonstrated to have a similar suppressive effect. The HIV lysate was not directly cytotoxic to lymphocytes and did not contain tumor necrosis factor or lymphotoxin. The HIV lysate specifically suppressed the proliferation of a range of hemopoietic cell lines from man and mouse including three EBV transformed CD4- and IL-2 receptor-negative B-cell lines. The lysate also suppressed the formation of human bone marrow colonies, whereas the lysate had only a slight or no effect on fibroblasts. The suppression of lymphocyte proliferation was not abrogated by addition of IL-2 or IL-1 and the HIV lysate inhibited the expression of IL-2 receptors on suboptimal PHA-stimulated mononuclear cells. The suppressive factor(s) has not been characterized in molecular terms, but suppressive activity was recovered in fractions with a molecular weight of about 67,000 and in both the glycoprotein fraction and in the glycoprotein-depleted fraction of the HIV lysate. Sera from one-third of a small series (N = 13) of individuals with antibodies to HIV seem to be able to neutralize the suppressive properties of HIV lysate in cultures.
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PMID:Investigation of immunosuppressive properties of inactivated human immunodeficiency virus and possible neutralization of this effect by some patient sera. 278 62

The effect of tumor necrosis factor (TNF) on the replication of human immunodeficiency virus type 1 (HIV-1) was investigated in several T4 lymphocyte cell lines. TNF markedly enhanced the cytopathogenicity of HIV-1, virion-associated reverse transcriptase (RT) activity in the cell culture supernatant, and viral antigen expression in MOLT-4 cells as early as 3 days after HIV-1 infection. A slight increase in RT activity was also observed in the supernatant of H9 cell cultures exposed to TNF. However, TNF did not increase either RT activity in MT-4 cell supernatants or viral antigen expression in HUT-78 cells. Thus, TNF is able to stimulate the replication of HIV-1 in de novo infected T4 cells although not all T4 cells seem to be sensitive to this stimulatory effect.
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PMID:Tumor necrosis factor enhances replication of human immunodeficiency virus (HIV) in vitro. 291 52

Treatment of cells with tumor necrosis factor-alpha and interferon-gamma greatly reduces their susceptibility to infection with human immunodeficiency virus and suppresses the production of human immunodeficiency virus (HIV) mRNA, core protein p24, and infectious HIV. The combination treatment is cytotoxic for HIV-infected cells and reduces HIV RNA levels in chronically infected cells.
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PMID:In vitro anti-human immunodeficiency virus activities of tumor necrosis factor-alpha and interferon-gamma. 312 35

The effect of culture supernatant of MT-2 cells on human immunodeficiency virus (HIV)-producing cells, MOLT-4/HIVHTLV-IIIB cells, was examined. As compared to the effect on MOLT-4 cells, parent cells not infected with HIV, a selective cytotoxic/cytostatic effect on MOLT-4/HIVHTLV-IIIB cells was observed 4 days after treatment with up to 640-fold-diluted MT-2 supernatant. Furthermore, under similar conditions, a 2- to 6-fold increase in the number of HIV particles was detected in the culture of MOLT-4/HIVHTLV-IIIB cells 6 hr after treatment. Complete blocking of these effects by anti-lymphotoxin monoclonal antibody, but not by anti-tumor necrosis factor antibody, indicates that these effects of MT-2 supernatant on MOLT-4/HIVHTLV-IIIB cells are attributable to a lymphotoxin-related cytotoxic factor.
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PMID:Effect of culture supernatant of MT-2 cells on human immunodeficiency virus-producing cells, MOLT-4/HIVHTLV-IIIB cells. 313 Mar 48

Studies of the biology and pathogenesis of Kaposi's sarcoma (KS) have been hampered by the inability to maintain long-term cultures of KS cells in vitro. In this study AIDS-KS-derived cells with characteristic spindle-like morphology were cultured with a growth factor (or factors) released by CD4+ T lymphocytes infected with human T-lymphotropic virus type I or II (HTLV-I or HTLV-II) or with human immunodeficiency virus type 1 or 2 (HIV-1 or HIV-2). Medium conditioned by HTLV-II-infected, transformed lines of T cells (HTLV-II CM) contained large amounts of this growth activity and also supported the temporary growth of normal vascular endothelial cells, but not fibroblasts. Interleukin-1 and tumor necrosis factor-alpha stimulated the growth of the KS-derived cells, but the growth was only transient and these could be distinguished from that in HTLV-II CM. Other known endothelial cell growth promoting factors, such as acidic and basic fibroblast growth factors and epidermal growth factor, did not support the long-term growth of the AIDS-KS cells. The factor released by CD4+ T cells infected with human retroviruses should prove useful in studies of the pathogenesis of KS.
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PMID:Kaposi's sarcoma cells: long-term culture with growth factor from retrovirus-infected CD4+ T cells. 326 25

A model system for cytokine-induced up-regulation of human immunodeficiency virus type 1 (HIV-1) expression in chronically infected promonocyte clones was established. The parent promonocyte cell line U937 was chronically infected with HIV-1 and from this line a clone, U1, was derived. U1 showed minimal constitutive expression of HIV-1, but virus expression was markedly up-regulated by a phytohemagglutinin-induced supernatant containing multiple cytokines and by recombinant granulocyte/macrophage colony-stimulating factor alone. Recombinant interleukin-1 (IL-1), IL-2, interferon-gamma, and tumor necrosis factor-alpha did not up-regulate virus expression. Concomitant with the cytokine-induced up-regulation of HIV-1, expression of membrane-bound IL-1 beta was selectively induced in U1 in the absence of induction of other surface membrane proteins. This cytokine up-regulation of IL-1 beta was not seen in the uninfected parent U937 cell line. These studies have implications for the understanding of the mechanism of progression from a latent or low-level HIV-1 infection to a productive infection with resulting immunosuppression. In addition, this model can be used to delineate the potential mechanisms whereby HIV-1 infection regulates cellular gene expression.
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PMID:Cytokine-induced expression of HIV-1 in a chronically infected promonocyte cell line. 331 29

Examination of the interaction between human immunodeficiency virus (HIV) regulatory gene products and the host immune system is fundamental to understanding the pathogenesis of HIV and could reveal possible targets for therapeutic intervention in the treatment of AIDS. The HIV Tat gene is a potential candidate for this type of strategy. Transgenic mice can be used to investigate the in vivo effects of Tat on the developing and dynamic immune system and on cellular gene expression. Thus, we have generated transgenic mice that harbor the HIV type 1 Tat gene under the transcriptional control of the human CD2 gene regulatory elements. This expression cassette results in high-level, tissue-specific transcription of the transgene within the T-cell compartment. In this report, we demonstrate the effects of Tat on the in vivo immune system. CD2-Tat transgenic mice show no signs of aberrant thymic development and have normal levels of T-cell subsets in the thymus and peripheral lymphoid organs. However, activated T cells from transgenic mice contain increased levels of tumor necrosis factor beta mRNA as well as biologically active tumor necrosis factor protein and express elevated levels of transforming growth factor beta and interleukin-4 receptor mRNA. These increased cytokine levels do not appear to alter mitogen- or antigen-stimulated responses or induce the formation of dermal lesions in ageing mice. Such investigations should provide insight into the combination of host immune factors mediating pathogenesis in HIV infection.
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PMID:Altered cytokine expression in T lymphocytes from human immunodeficiency virus Tat transgenic mice. 749 70

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

Infection with several DNA or RNA viruses induces a state of increased sensitivity to cell lysis mediated by tumor necrosis factor (TNF), particularly in the presence of gamma interferon (IFN-gamma). Infection of human cells with the human immunodeficiency virus (HIV) may induce a similar phenomenon. However, TNF and IFN-gamma are known upregulators of HIV replication, raising the question of the potential role of these cytokines in the selective elimination of cells infected with this virus. The present study demonstrates that chronically infected U1 cells were killed with much greater efficiency by costimulation with TNF-alpha and IFN-gamma than their uninfected parental cell line U937. However, synergistic induction of viral expression also occurred in U1 cells as a consequence of treatment with the two cytokines. Cell death in U1 cells was not caused by the massive production of virions, in that costimulation with glucocorticoid hormones and TNF-alpha or IFN-gamma resulted in high levels of virion production without cytopathicity. To investigate the nature of the selective cytotoxic effect observed in U1 cells costimulated with TNF-alpha plus IFN-gamma, a panel of uninfected cell clones was generated by limiting dilution of U937 cells and tested for response to TNF-alpha and/or IFN-gamma. In contrast to the uncloned bulk parental U937 cell line, most uninfected cell clones showed a very high susceptibility to being killed by TNF-alpha and IFN-gamma. Similar findings were obtained when both infected U1 cells and several uninfected U937 cell clones were costimulated with an anti-Fas monoclonal antibody in the presence of IFN-gamma, although, unlike cells stimulated with TNF-alpha, cells treated with anti-Fas antibody did not express virus. Therefore, the increased susceptibility to cytokine-mediated lysis observed in cell lines infected with HIV is likely due to the selection of preexisting cell clones rather than viral infection.
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PMID:Cytokine-mediated induction of human immunodeficiency virus (HIV) expression and cell death in chronically infected U1 cells: do tumor necrosis factor alpha and gamma interferon selectively kill HIV-infected cells? 751 Nov 75


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