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)

Progression of HIV-induced immunodeficiency is associated with both B cell activation and an increased proportion of Vdelta1+ T cells in PBL. To examine whether the peripheral expansion of Vdelta1+ cells is driven by activated B cells, we isolated CD19+ PBL from HIV+ individuals at different stages of infection and used them to stimulate Vdelta1+ T cell clones. The Vdelta1+ T cell clones were isolated from HIV+ individuals and selected on the basis of cytotoxic activity and IFN-gamma expression in response to lymphoblastoid cell lines (LCLs) established from patients with AIDS (AIDS-related LCLs) but not LCLs of HIV- donors. Peripheral blood B cells from HIV+ patients induced IFN-gamma expression in these Vdelta1+ clones, and their stimulatory ability was associated with up-regulated expression of the CD38 activation Ag and with a 6- to 10-fold increased spontaneous Ig production. Stimulation of CD19+ PBL from HIV+ individuals with cross-linked anti-CD40 mAb or rgpl20 further augmented induction of IFN-gamma expression in the Vdelta1+ cells. The isolated Vdelta1+ T cell clones expressed the Jdelta1 gene segment, but differed in Vgamma gene segment usage and in the junctional region of TCR-delta chains, indicating Vdelta gene-determined recognition. These results provide evidence that the peripheral expansion of Vdelta1+ cells in HIV infection is associated with phenotypic and functional alterations of B cells, due to chronic activation during progression to AIDS.
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PMID:Evidence for B cell-mediated activation of V delta 1+ T lymphocytes during progression of HIV infection. 897 24

Cytokine mRNA expression and stimulus-induced cytokines were examined in peripheral blood mononuclear cells in 62 human immunodeficiency virus (HIV)-infected children and uninfected controls. Compared with that in controls, constitutive mRNA expression in patients was increased for tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and interleukin (IL)-10 and decreased for IL-12; it was undetectable for IL-2 and IL-4 in both patients and controls. Stimulus-induced secretion of TNF-alpha, IFN-gamma, IL-12, and IL-4 was less than that in controls; IL-10 secretion was similar. There was no increase in stimulus-induced or constitutive IL-4 or IL-10 in children with severe immunologic deficit compared with controls. A higher stimulus-induced IL-10 secretion and a lower constitutive TNF-alpha mRNA were associated with a slower rate of disease progression, and TNF-alpha mRNA expression correlated with lower plasma HIV RNA. Thus, constitutive cytokine mRNA expression differs from stimulus-induced cytokine responses. The dominant defect in HIV-infected children appears to be one of reduced type 1 cytokines, predominantly IL-2.
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PMID:Cytokine pattern in relation to disease progression in human immunodeficiency virus-infected children. 898 95

Interleukin 15 (IL-15) is a cytokine that shares receptor subunits and functional activity, such as T-cell and B-cell stimulation, with IL-2. The effect of IL-2 on immune function and human immunodeficiency virus (HIV) viral load in HIV-infected patients is being actively studied. Thus, we examined how IL-15 compares with IL-2 in several in vitro immunologic and virologic assays in order to explore whether a rationale exists for pursuing initial clinical therapeutic trials with IL-15. The effects of IL-15 on induction of lymphokine-activated killer (LAK) cells, gamma interferon (IFN-gamma) production from HIV-positive peripheral blood mononuclear cells (PBMCs), and HIV production from PBMCs were studied. Induction of LAK cells by IL-15 was found in eight of eight HIV-positive donors. Incubation of PBMCs from some donors with IL-15 (1, 10, 50, and 100 ng/ml) induced production of IFN-gamma. The effect of IL-15 was compared with that of IL-2 on HIV replication in PBMCs from five HIV-positive patients and four HIV-negative donors whose PBMCs were infected in vitro with HIV. Levels of HIV p24 antigen were moderately lower in the presence of 10 ng of IL-15 per ml than with 10 ng of IL-2 per ml, but they were similar for 100 and 500 ng of each cytokine per ml. In summary, IL-15 can induce LAK cell activity in HIV-seropositive patients and can stimulate IFN-gamma production from PBMCs of some donors. IL-15 stimulates levels of HIV production from PBMCs which are similar to or moderately lower than those obtained with IL-2, depending on cytokine concentration.
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PMID:In vitro immunologic and virologic effects of interleukin 15 on peripheral blood mononuclear cells from normal donors and human immunodeficiency virus type 1-infected patients. 900 79

Impairment of interferon (IFN) system in human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) became a basis for searching IFN responses to monitor the disease progression. For detailed investigations 16 HIV+/AIDS patients with at least 4 successively taken blood samples available for IFN determinations were selected. IFN responses were tested in two ways. Firstly, IFN level in plasma was measured. Secondly, capacity of IFN production by leukocytes was evaluated. The latter was determined in the whole blood assay, in which Newcastle disease virus (NDV) and phytohemagglutinin (PHA) were used as IFN-alpha and IFN-gamma inducers, respectively. The levels of IFN induced in whole blood leukocytes varied considerably in all individuals that had been tested. Nevertheless, two patterns of IFN responses were observed. In pattern I, patients had low levels of IFN in plasma and high levels of induced IFN-alpha and IFN-gamma. It was characteristic for 8 patients in good clinical condition. On the contrary, severe disease found in 2 patients was correlated with high levels of IFN in plasma and low levels of induced IFNs (pattern II). In 6 patients IFN responses were classified as intermediate pattern I/II suggesting transition from pattern I to pattern II. A variation of pattern I was found in the case of a patient defined as long-term survivor having relatively low levels of all IFN tested. The results suggested that interferon measurements reflected clinical condition of HIV+ patients showing not only past but also current immune changes.
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PMID:Long-term assessment of interferon responses in the HIV+ and AIDS patients. 901 50

Simian immunodeficiency virus (SIV) replication is rapidly downregulated in the lymph nodes (LN) of rhesus macaques after the acute stage of primary infection. The aim of this study was to evaluate a possible role of interferon-gamma (IFN-gamma) in the control of SIV replication. IFN-gamma expression was analysed by in situ hybridization in the LN of rhesus macaques that were inoculated either with a high dose or with a low dose of the pathogenic isolate SIVmac 251. The kinetics of IFN-gamma induction in LN was found to follow that of SIV replication. However, the number of IFN-gamma expressing cells was not proportional to the number of infected cells. IFN-gamma expression in LN was further quantified by competitive RT-PCR. The number of IFN-gamma mRNA molecules in LN was high for the animals of the high dose group. In the low dose group, the IFN-gamma copy number varied over 2 log10 units and was particularly low for the animals that had a high and persisting antigenaemia. The analysis of a total of 10 animals inoculated with a low dose of virus showed an inverse correlation between IFN-gamma expression in LN and peak antigenemia (P < 0.01). This study provides evidence for a marked individual variability in the IFN-gamma response to primary SIV infection and supports the notion that IFN-gamma production is inhibited at an early stage in animals that harbour a high viral load.
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PMID:Interferon-gamma expression in macaque lymph nodes during primary infection with simian immunodeficiency virus. 904 81

It is supposed that Leishmania infection increases human immunodeficiency virus (HIV) replication in seropositive individuals. Two groups of 9 HIV-infected intravenous drug users each, one group with HIV-Leishmania coinfection (as determined by bone marrow microscopy, culture and an immunofluorescent assay, the other with HIV infection alone, but no evidence of Leishmania coinfection were matched for sex, age, time since first diagnosis of HIV infection, number of AIDS-defining diseases, proportion of patients treated with AZT and months of treatment, CD4/CD8 ratio, beta 2-microglobulin level and HIV p24 antigen positivity rate. IL-4, -6, -10 and -12 and IFN-gamma levels were determined by commercial enzyme immunoassays. The HIV-1 RNA copy number was quantified with the nucleic-acid-sequence-based amplification method (NASBA). The differences between the two groups were highly significant for all markers determined except for IL-12 and IFN-gamma. We found a higher viral load in the patients with HIV-Leishmania coinfection compared to the patients with HIV infection alone (p < 0.009). In 6 HIV-positive individuals without Leishmania coinfection, the HIV-1 RNA copy number was below the detection limit of NASBA (i. e. < 400 copies/100 microliters). Plasma levels of IL-4, -6, and -10 were significantly elevated in the coinfected group (p < 0.0001; p < 0.02, and p < 0.005). The results of our study show that the viral load is increased in patients with HIV-Leishmania coinfection in comparison to the controls. This might be partly due to Th2 immune activation, as demonstrated by higher plasma levels of IL-4, -6 and -10 in HIV-Leishmania-coinfected patients than in HIV-infected individuals.
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PMID:Immunological findings in HIV-Leishmania coinfection. 907 71

We have engineered recombinant vaccinia virus vectors expressing murine interleukin-7 (IL-7) in order to study the activity of this factor during virus infection. Virus-encoded IL-7 dramatically increased splenic cellularity in infected mice and enhanced the proliferative activity of T cells and their capacity to secrete IL-2 and IL-6, but not IFN-gamma, TNF-alpha or IL-4. Numbers of splenic CD4+ and CD8+ T lymphocytes were elevated two- to threefold. IL-7 also mediated a marked enhancement of both antigen-specific and nonspecific cellular immune activity. Total splenic antiviral cytotoxic T cells (CTL), natural killer (NK), and lymphokine-activated killer cells (LAK) responses were augmented significantly in mice given VV-HA-IL-7 compared with those given control virus, with accelerated clearance of the former. The enhanced antiviral cellular immune activity mediated by IL-7 was critically dependent on IL-2 produced by the host, but occurred independently of IFN-gamma. The ability of IL-7 to induce cellular immune responses in vivo may have applications in antiviral immunotherapy, particularly in cases of immunodeficiency.
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PMID:Interleukin-7 enhances cell-mediated immune responses in vivo in an interleukin-2-dependent manner. 909 26

Indoleamine 2,3-dioxygenase (IDO) and nitric oxide synthase (NOS) type II are induced in macrophages by interferon (IFN)-gamma and lipopolysaccharide (LPS). Nitric oxide has been previously shown to inhibit IDO activity. We studied whether metabolites of tryptophan via the IDO pathway could alter NOS II activity. In RAW 264.7 cells, the phenolic antioxidant 3-hydroxyanthranilic acid (OH-AA), but not anthranilic acid, inhibited citrulline synthesis by NOS II at sub-millimolar concentrations, when added 1 h before IFN-gamma and LPS. OH-AA inhibited NOS II activity in cytosolic extracts, suggesting a direct action of OH-AA on NOS II protein. Moreover, expression of NOS II mRNA and activation of the nuclear factor kappa B (NF-kappa B) in RAW 264.7 cells were decreased by a pretreatment with OH-AA, but not anthranilic acid, before addition of IFN-gamma and LPS. This pretreatment also inhibited activation of NF-kappa B in response to TNF-alpha in lymphoblastoid J.Jhan5-1 cells. Finally, expression of a long terminal repeat of the human immunodeficiency virus (HIV-LTR)-driven luciferase reporter gene, controlled by NF-kappa B activation, was severely decreased by OH-AA or 3-hydroxykynurenine in J.Jhan5-1 cells. Other tryptophan derivatives were inactive. These data identify OH-AA as an aminophenolic tryptophan derivative inhibiting NF-kappa B activation and impairing both NOS II expression and activity in a millimolar concentration range.
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PMID:Inhibition of nitric oxide synthase expression and activity in macrophages by 3-hydroxyanthranilic acid, a tryptophan metabolite. 912 84

The MHC class II transactivator gene (CIITA) coordinately controls the expression of the three major human class II genes, HLA-DR, HLA-DQ, and HLA-DP. Indeed, patients with one form of MHC class II immunodeficiency disease, due to defective CIITA genes, lack expression of all three isotypes. Nevertheless, there is substantial evidence that human class II genes are not always coordinately regulated, raising the possibility that CIITA-independent, isotype-specific class II regulatory pathways exist. To address this issue, we have generated a dominant negative mutant of CIITA that lacks the acidic transcription-activating N terminus, but retains the proline/serine/threonine-rich domain. Three newly produced anti-CIITA mAbs revealed that this mutant protein lacked N-terminal epitopes. In this study, we report that this CIITA dominant negative mutant repressed the constitutive expression of all three class II isotypes in human EBV-B cell lines, as well as IFN-gamma-induced class II transcription in HeLa cells. However, in a CIITA-deficient, EBV-transformed B cell line, clone 13, the dominant negative mutant did not alter the endogenous expression of the HLA-DQ gene. Taken together, these data demonstrate the existence of both CIITA-dependent and -independent class II regulatory pathways. Furthermore, our data provide evidence that the latter pathways can be isotype specific.
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PMID:CIITA-dependent and -independent class II MHC expression revealed by a dominant negative mutant. 914 88

CD8+ T-cell clones were generated from peripheral blood mononuclear cells (PBMC) of three human immunodeficiency virus (HIV)-seronegative individuals and six HIV-seropositive individuals and assessed for their cytokine secretion profile, cytolytic potential, and chemokine production. While the great majority of CD8+ T-cell clones generated from HIV-seronegative individuals produced interferon (IFN)-gamma, but not interleukin-4 (IL-4), that is a type 1 cytotoxic (Tc1) profile, high numbers of CD8+ T-cell clones generated from HIV-seropositive individuals produced IL-4 in addition to IFN-gamma or IL-4 alone, thus showing a type 0 cytotoxic (Tc0)- or a type 2 cytotoxic (Tc2) profile, respectively. Tc0/Tc2 cells displayed lower cytolytic activity than Tc1 cells, including a reduced ability to lyse autologous targets pulsed with HIV or HIV peptides. By contrast, the production of chemokines RANTES and macrophage inflammatory protein-1alpha was comparable in Tc1, Tc0, and Tc2 clones irrespective of whether they were derived from HIV-seronegative or HIV-seropositive individuals. When CD8+ T-cell clones were generated from PBMC cultures of HIV-seronegative individuals conditioned with IL-4 plus an anti-IL-12 antibody (Ab), a shift towards the Tc0/Tc2-like profile was observed. Conversely, the addition to PBMC cultures of IL-12 plus an anti-IL-4 Ab shifted the differentiation of CD8+ T cells from HIV-infected individuals towards the Tc1-like profile, whereas IL-12 or anti-IL-4 Ab alone had a lower Tc1-promoting effect. Irradiated PBMC from HIV-infected individuals, used as feeder cells, shifted the differentiation of CD8+ T cells from a healthy HIV-seronegative individual towards the Tc0/Tc2-like profile. On the other hand, a shift towards the Tcl-like profile was noted in CD8+ T-cell clones generated from the skin specimens of two HIV-seropositive patients with Kaposi's sarcoma, successfully treated with IFN-alpha, in comparison to CD8+ clones generated from the same skin areas before treatment. The IFN-alpha-induced Tc1 shift could be prevented by the incubation of skin-infiltrating CD8+ T cells with IL-4 before cloning. Taken together, these data indicate that both defective production of IL-12 and abnormal IL-4 production in bulk PBMC populations of HIV-infected individuals may contribute to the development of high numbers of CD8+ T-cell clones showing a Tc0/Tc2-like phenotype and reduced cytolytic potential against HIV itself. They also suggest that the cytokine profile of CD8+ T-cell clones can be modulated by cytokines (or anticytokine Ab) both in vitro and in vivo.
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PMID:Functional characterization and modulation of cytokine production by CD8+ T cells from human immunodeficiency virus-infected individuals. 916 Jun 72


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