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)

Live-attenuated simian immunodeficiency virus (SIV) protects macaques against challenge with pathogenic SIV. To evaluate the safety of such vaccines, an investigation of whether or not nef-deleted SIV could be reactivated in vivo by immune activation of the host was conducted. In addition, monkeys infected with apathogenic SIV/HIV-1 chimeric viruses, and two control monkeys that had suppressed replication of pathogenic SIV were examined. During the infection virus became undetectable or persisted at a low level of replication in all monkeys. At this time-point 11 monkeys were immune-activated by a vaccinia virus (VV) superinfection. After VV infection up to 80% of their lymphocytes showed expression of the activation markers CD25 and CD69 over 2 weeks. However, only the two non-progressing monkeys infected with pathogenic SIV showed a noticeable but transient enhancement of SIV replication and increased SIV antibody titres. By contrast, in monkeys infected with apathogenic immunodeficiency viruses no change in virus load was observed. Therefore, attenuated immunodeficiency viruses cannot be reactivated in vivo by a VV-induced immune activation.
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PMID:No reactivation of attenuated immunodeficiency viruses in rhesus macaques after vaccinia virus-induced immune activation. 934 73

Peripheral blood mononuclear cells were prepared from human immunodeficiency virus-positive (HIV+) individuals (n = 46) to investigate the expression of both chains of the interleukin-2 receptor. Both qualitative and quantitative changes in expression were observed. Total lymphocyte expression of the IL-2 alpha chain (CD25) was decreased compared with HIV-negative (HIV-) controls. This was due to the decrease in the CD4+ population, which favored expression of this receptor, rather than a decrease in expression, per se. CD8+ lymphocytes expressed the beta chain (CD122) in the absence of the alpha chain. However, a significant increase in the number of peripheral blood CD8+ lymphocytes expressing mainly the beta subunit was observed in HIV+ patients (P = 0.02). This was observed to a similar extent in asymptomatic and symptomatic patients and characterized a subpopulation of T lymphocytes expressing high levels of CD8. Lymphocytes from patients with advanced HIV disease failed to up-regulate both alpha and beta chains in response to mitogenic concentrations of phytohaemagglutanin. However, those cells that were able to up-regulate both of the IL-2 receptors were capable of effective signal transduction through the receptor, increasing the proliferative response to stimulation.
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PMID:Dysregulation of the interleukin-2 receptor alpha- and beta-chain expression in CD4 and CD8 T cells in HIV infection. 944 Aug 20

Cartilage hair hypoplasia is a rare autosomal recessive form of short-limbed dwarfism associated with a cellular immunodeficiency. In eight patients, the authors studied the presence of T cell subsets and in vitro T cell function in order to address the basis for the immunological disorder. Both the proliferative response to phytohaemagglutinin (PHA) and the PHA-induced IL2 production were 60% lower compared with controls (P = 0.007 and 0.005, respectively). The impaired proliferative response could not be restored by addition of IL-2. This result is in accordance with a decrease in the percentage of activated T cells expressing the p55 subunit of the IL-2 receptor complex (CD25). The results define more precisely that T cells from cartilage hair hypoplasia patients are defective in the transition from the G0 to the G1 phase of the cell cycle. Furthermore, the data demonstrate that several CHH patients show a reduced proportion of CD45RA+ 'naive' T cells. However, the in vitro impairment of T cell function cannot solely be explained by imbalance between 'naive' and 'memory' T cells. Although CHH patients with a history of recurrent respiratory tract infections showed the most aberrant in vitro immune parameters, a clear relationship between clinical data and in vitro parameters could not be established for the whole patient group.
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PMID:T cell subsets and T cell function in cartilage-hair hypoplasia. 958 3

The first step in the replication of human immunodeficiency virus (HIV) is selective binding of the envelope glycoprotein (gp120) to CD4 receptors on T cells or macrophages. After penetration in these cells, the genome of the virus is integrated in the human genome. HIV-infection causes depletion of CD4-positive cells resulting in a severe immunosuppression. It is believed that eliminating HIV-infected cells is crucial in limiting further reduction of CD4-positive cells and thus, preventing disease progression. The most commonly used drugs, such as zidovudine (AZT), appeared to be not completely effective. Therefore many investigators are searching for alternative treatment modalities. The use of immunotoxins (ITs) to eliminate HIV-infected cells is discussed. ITs are chimeric molecules in which cell-binding ligands are coupled to toxins and can specifically eliminate undesired cells. The cell-binding carriers of anti-HIV ITs have been directed against different regions of the HIV envelope glycoprotein (gp120 and gp41) and surface antigens (e.g CD4, CD25). The ITs have been composed of different ribosome-inactivating proteins (RIPs) like pokeweed antiviral protein (PAP), Pseudomonas exotoxin (PE), Diphtheria toxin (DT), or ricin. In in vitro studies, several of these ITs have been shown to be effective and specific in killing acute and persistently HIV-infected cells. The ITs were effective at concentrations (ID50 range from 10(-9) M to 10(-12) M) that were not toxic to uninfected cells or cells without the antigen. The IT CD4(178)PE40, a fusion protein directed against the CD4 binding site of gp120, has been investigated in two in vivo trials. The results were disappointing considering the antiviral activity in vitro. This was thought to be due to the rapid clearance of the IT and the differential resistance of clinical HIV isolates. Use of a panel of ITs is likely to be more effective because multiple approaches cover the intrinsic variability of HIV and the presence of IT-resistant or latently infected cells, as well as the blocking presence of neutralizing anti-HIV antibodies and the immunogenicity of most ITs. It may be possible to control the virus completely with a panel of ITs in combination with other antiviral or immunosuppressive agents such as RT inhibitors (e.g AZT), interferon alpha, or cyclosporine. More research will be necessary to develop such a combined therapy.
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PMID:Rationale for the use of immunotoxins in the treatment of HIV-infected humans. 958 64

Sooty mangabeys naturally infected with simian immunodeficiency virus (SIV) do not develop immunodeficiency despite the presence of viral loads of 10(5) to 10(7) RNA copies/ml. To investigate the basis of apathogenic SIV infection in sooty mangabeys, three sooty mangabeys and three rhesus macaques were inoculated intravenously with SIVmac239 and evaluated longitudinally for 1 year. SIVmac239 infection of sooty mangabeys resulted in 2- to 4-log-lower viral loads than in macaques and did not reproduce the high viral loads observed in natural SIVsmm infection. During acute SIV infection, polyclonal cytotoxic T-lymphocyte (CTL) activity coincident with decline in peak plasma viremia was observed in both macaques and mangabeys; 8 to 20 weeks later, CTL activity declined in the macaques but was sustained and broadly directed in the mangabeys. Neutralizing antibodies to SIVmac239 were detected in the macaques but not the mangabeys. Differences in expression of CD38 on CD8(+) T lymphocytes or in the percentage of naive phenotype T cells expressing CD45RA and CD62L-selection did not correlate with development of AIDS in rhesus macaques. In macaques, the proportion of CD4(+) T lymphocytes expressing CD25 declined during SIV infection, while in mangabeys, CD25-expressing CD4(+) T lymphocytes increased. Longitudinal evaluation of cytokine secretion by flow cytometric analysis of unstimulated lymphocytes revealed elevation of interleukin-2 and gamma interferon in a macaque and only interleukin-10 in a concurrently infected mangabey during acute SIV infection. Differences in host responses following experimental SIVmac239 infection may be associated with the divergent outcome in sooty mangabeys and rhesus macaques.
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PMID:Diverse host responses and outcomes following simian immunodeficiency virus SIVmac239 infection in sooty mangabeys and rhesus macaques. 981 93

To test the hypothesis that coinfection with human immunodeficiency virus (HIV) and human T cell leukemia/lymphoma virus types I or II (HTLV-I or -II) accelerates progression to AIDS, pig-tailed macaques were inoculated with the simian counterparts, SIV and STLV-I. During 2 years of follow-up of singly and dually infected macaques, no differences in SIV burdens, onset of disease, or survival were detected. However, in the first coinfected macaque that died of AIDS (1 year after infection), >50% of CD4+ and CD8+ lymphocytes expressed CD25. On the basis of the low incidence of HTLV-I- and STLV-I-associated disease during natural infections, this early evidence of neoplastic disease was unexpected. While these results demonstrate that coinfection with SIV and STLV-I has no influence on the development of immunodeficiency disease, they do establish a reliable macaque model of persistent STLV-I infection.
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PMID:Coinfection of macaques with simian immunodeficiency virus and simian T cell leukemia virus type I: effects on virus burdens and disease progression. 995 66

Determining the effects of HIV infection on the expression of cell surface molecules has been limited by an inability to differentiate between productively infected cells and those without productive infection. We inoculated human peripheral blood mononuclear cells from healthy, human immunodeficiency virus type 1 (HIV) antibody-negative donors with HIV; noninoculated cells were also examined. Using multiparameter flow cytometry, we differentiated cells actively producing HIV cytoplasmic p24 antigen during acute, in vitro HIV infection from those not producing detectable cytoplasmic p24. For both resting and PHA-stimulated cells inoculated with HIV (R/H and P/H), a higher proportion of p24+ cells expressed CD25, compared with p24-cells (p = 0.031 and p = 0.008, respectively), consistent with either increased viral replication in stimulated cells or increased stimulation secondary to productive HIV infection. Findings were similar for the expression of CD38, HLADR, and CD28. A striking proportion of p24+ cells expressed CD80 or CD86, antigens not usually expressed by CD3+ lymphocytes. The increased expression appeared to be independent of stimulation status in that it occurred in both the R/H and P/H treatment groups but not in resting or PHA-stimulated uninfected cells. CD28 expression was generally comparable between CD3+ cells that did and did not express CD80 or CD86. Multiparameter flow cytometry, in association with improved techniques for cell permeabilization and cytoplasmic fluorescent staining, should prove useful in examining the effects of productive HIV infection on surface and cytoplasmic cellular molecules. Using this approach, we found an association between productive infection and increased expression of CD80 and CD86. This association has implications for HIV disease pathogenesis and, potentially, HIV therapy.
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PMID:Increased expression of CD80 and CD86 in in vitro-infected CD3+ cells producing cytoplasmic HIV type 1 p24. 1002 49

Interleukin-16 (IL-16), a natural ligand for the CD4 receptor, has been found to modulate T-lymphocyte function and to inhibit human immunodeficiency virus type 1 (HIV-1) replication. Antigen-presenting cells (APC), including macrophages and dendritic cells, are known to express functional surface CD4 molecules, to be susceptible to HIV-1 infection and to play a critical role in different immune processes. Therefore, we evaluated the ability of recombinant IL-16 (rIL-16) to regulate receptor expression and cytokine release in monocyte-derived macrophages (MDM) and monocyte-derived dendritic cells (MDDC). Recombinant IL-16 was found to up-regulate CD25 and CD80 but to down-regulate CD4 and CD86 surface expression in MDM cultures. However, no change could be observed on the level of CD4, CD80 and CD86 expression in IL-16-stimulated MDDC, although a significant up-regulation of CD25 and CD83 was consistently detected. Furthermore, the level of gene expression of the chemokine receptors CCR5 and CXCR4 was significantly reduced in rIL-16-treated MDM and costimulation with IL-2 did not modify the activity of the recombinant cytokine. The effects on chemokine receptor gene expression were less evident in MDDC and only a transient down-regulation of weak intensity could be detected following stimulation with rIL-16. Analysis of supernatants from rIL-16-stimulatedcultures revealed a different profile of released cytokines/chemokines among the two cell populations studied. These findings establish an important role for IL-16 in modulating the activity of APC and may have relevance regarding the protection of reservoir cells against HIV-1 infection.
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PMID:Recombinant interleukin-16 selectively modulates surface receptor expression and cytokine release in macrophages and dendritic cells. 1044 38

Chronic immune activation by coinfecting pathogens has been suggested as a cofactor in human immunodeficiency virus (HIV) disease progression, particularly in the setting of developing countries. Here, we used in vivo-infected mononuclear cells to examine the role of the protozoan parasite Leishmania donovani and its major membrane constituent, lipophosphoglycan (LPG), in mediating CD4+ T-lymphocyte activation-induced HIV replication and CD4+ T-cell death. We found that Leishmania antigens upregulated HIV replication in CD8-depleted peripheral blood mononuclear cells from asymptomatic HIV-infected donors compared to unstimulated cells. L. donovani-induced viral replication was associated with cellular proliferation, increased expression of the cellular immune activation markers CD25 and HLA-DR within the CD4+ subpopulation, and enhanced secretion of tumor necrosis factor alpha (TNF-alpha), interleukin 2 (IL-2), and IL-6. LPG induced TNF-alpha secretion in the absence of increased expression of cellular activation markers. Moreover, in a few cases we observed that L. donovani induced HIV replication without significant cellular activation but with cytokine secretion. The rate of apoptosis was accelerated in these latently infected CD4+ T cells primed with Leishmania antigens compared to controls, and TNF-alpha production appeared to be the central event necessary for this effect. Furthermore, we demonstrate that thalidomide inhibited Leishmania-induced virus replication coupled with abrogated Leishmania-induced TNF-alpha secretion but not IL-2 or IL-6 production. Furthermore, thalidomide did not affect Leishmania-induced apoptosis. The results suggest that Leishmania and its product, LPG, up-regulate HIV replication in latently infected cells through distinct antigen-specific and non-antigen-specific cellular immune activation mechanisms and that TNF-alpha secretion is pivotal in this process. The immunomodulatory role of thalidomide raises interest as a potential adjuvant to reduce HIV disease progression in Leishmania-HIV coinfected individuals.
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PMID:Role of Leishmania donovani and its lipophosphoglycan in CD4+ T-cell activation-induced human immunodeficiency virus replication. 1049 4

We have investigated the ability of anti-CD28 antibody costimulation to induce resistance to macrophage (M)-tropic strains of human immunodeficiency virus type 1 (HIV-1) in vitro. Our results confirm the observations of Levine et al. (15) that stimulation of CD4 T cells with anti-CD3/anti-CD28 antibodies coimmobilized on magnetic beads renders the cells resistant to infection by M-tropic strains of HIV-1. The resistance was strongest when the beads were left in the cultures throughout the experiment. In contrast, stimulation of CD4 T cells with the same antibodies immobilized on the surface of plastic culture dishes failed to induce resistance and resulted in high levels of p24 production. This was true even if the cells were passaged continuously on freshly coated plates. If the beads were removed after initial stimulation, p24 production increased over time and produced a result intermediate to the other forms of stimulation. For beads-in, beads-out, and one-time plate stimulated cultures, resistance to infection correlated with down-regulation of CCR5 expression at the cell surface and with increased production of beta-chemokines. However, cultures of CD4 T cells continuously passaged on anti-CD3/anti-CD28-coated plates produced large amounts of p24 despite decreased levels of CCR5 expression and increasing production of beta-chemokines. Expression of the T-cell activation markers CD25 and CD69 and production of gamma interferon further supported the differences in plate versus bead stimulation. Our results explain the apparent contradiction between the ability of anti-CD28 antibody costimulation to induce resistance to HIV infection when presented on magnetic beads and the increased ability to recover virus from the cells of HIV-positive donors who are on highly active antiretroviral therapy when cells are stimulated by anti-CD3/anti-CD28 immobilized on plastic dishes.
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PMID:The mode and duration of anti-CD28 costimulation determine resistance to infection by macrophage-tropic strains of human immunodeficiency virus type 1 in vitro. 1051 42


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