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)

Highly purified, small dense splenic B cells from unstimulated mice showed increased expression of class II major histocompatibility complex (MHC) antigens and enhanced viability when cultured with affinity-purified recombinant interleukin 10 (rIL-10), compared with B cells cultured in medium alone. These responses were blocked by a monoclonal antibody (mAb) specific for IL-10, but not by an isotype-matched control antibody. IL-10 did not upregulate the expression of Fc epsilon receptors (CD23) or class I MHC antigens on small dense B cells or induce their replication as monitored by [3H]thymidine incorporation. While these B cell-stimulatory properties of IL-10 are also mediated by IL-4, the two cytokines appear to act independently in these assays; anti-IL-10 antibodies blocked IL-10 but not IL-4-mediated B cell viability enhancement, and vice versa. Similarly, since IL-4 upregulates CD23 on small dense B cells, the inability of IL-10 to do so argues against its acting via endogenously generated IL-4. Finally, IL-10 did not upregulate class II MHC antigens on B cells from X chromosome-linked immunodeficiency (XID) mice, while the same cells showed normal upregulation of class II antigens in response to IL-4. This report also extends our understanding of the relationship between IL-10 and the highly homologous Epstein-Barr virus (EBV)-encoded Bam HI fragment C rightward reading frame no. 1 (BCRFI) protein. It has previously been shown that BCRFI protein exhibits the cytokine synthesis inhibitory activity of IL-10. This report indicates that BCRFI protein also enhances in vitro B cell viability, but does not upregulate class II MHC antigens on B cells. One explanation for these data is that IL-10 contains at least two functional epitopes, only one of which has been conserved by EBV.
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PMID:Interleukin 10, a novel B cell stimulatory factor: unresponsiveness of X chromosome-linked immunodeficiency B cells. 212 52

Low IgG production is a characteristic feature of both the immunodeficiency of recipients of bone marrow transplant (BMT) and the physiologic immunodeficiency of newborns. We tried to determine whether this is due to a B cell defect and whether this can be corrected in vitro by IgG production-promoting cytokines CD40 ligand (CD40L) and interleukin 10 (IL-10). Highly purified circulating B cells from patients at 1 year after transplant, normal neonates and normal adults were cultured with and without anti-mu plus CD40L plus IL-10. Proliferation was measured on day 4 and IgM and IgG production were measured on day 9. Proliferation and IgM production of B cells from patients and from neonates were somewhat low (43-67% of normal). In contrast, IgG production by B cells from patients and from neonates was markedly low (< or = 13% of normal). Decreased IgG production correlated with decreased percentage of B cells negative for membrane IgD (mIgD). We conclude that the low IgG production of normal neonates and patients at 1 year after transplant is, at least in part, caused by a defect of circulating B cells and that this defect cannot be corrected by CD40L and IL-10. Quantitative deficiency of switched mIgD-) B cells probably accounts for this defect.
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PMID:Low IgG production by mononuclear cells from marrow transplant survivors and from normal neonates is due to a defect of B cells. 767 Mar 95

The intrathecal synthesis of interleukin 10 (IL-10) was investigated in 120 paired cerebrospinal fluid (CSF) and serum specimens from patients with various inflammatory and non-inflammatory diseases of the central nervous system (CNS). IL-10 was not demonstrated in the sera, but detectable levels were found in the CSF from: patients with acute viral ("aseptic") meningitis, but only within 48-72 h of symptom onset; human immunodeficiency virus type 1 (HIV)-infected patients with HIV-related encephalitis/leukoencephalopathy or cryptococcal meningitis; a patient with primary B cell lymphoma of the CNS, and a patient with encephalomeningeal sarcoidosis (in whom IL-10 was demonstrated in all CSF collected over a period of 6-months). In chronic meningeal infections/inflammations, IL-10 seems to be continuously produced within the CSF. Our findings suggest that IL-10, a cytokine which exerts many immunosuppressive actions, may play different immunomodulatory roles in CNS diseases; in particular, its intrathecal synthesis may explain why some infectious and inflammatory meningeal diseases may have slow development and chronic evolution.
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PMID:Intrathecal synthesis of interleukin-10 (IL-10) in viral and inflammatory diseases of the central nervous system. 783 46

In monocytes, the nuclear factor NF-kappa B has been invoked as an important transcription factor in the expression of cytokine genes, of cell-surface receptors and in the expression of human immunodeficiency virus. In such cells, DNA binding activity of NF-kappa B can be detected without intentional stimulation. In our studies, cells of the human monocytic line Mono Mac 6, cultured in medium containing fetal-calf serum and low levels of lipopolysaccharide (LPS), also exhibit such 'constitutive' NF-kappa B, as demonstrated by mobility-shift analysis of nuclear extracts. This nuclear NF-kappa B was still present when contaminant LPS was removed by ultrafiltration and when serum was omitted. Protein-DNA complexes of constitutive NF-kappa B are similar in mobility to the LPS-induced NF-kappa B and both are recognized by an antibody specific to the p50 subunit of NF-kappa B. By contrast, treatment of cells with pyrrolidine dithiocarbamate (PDTC) will only block LPS-induced NF-kappa B, but not the constitutive binding protein. Using LPS-free and serum-free conditions, constitutive NF-kappa B can be detected in different cell lines of the monocytic lineage (HL60, U937, THP-1, Mono Mac 1 and Mono Mac 6), but not in Molt 4 T cells or K562 stem cells. When ordered according to stage of maturation, the amount of constitutive NF-kappa B was not increased in more mature cell lines. Furthermore, when inducing differentiation in Mono Mac 6 cells, with vitamin D3, no change in constitutive or inducible NF-kappa B can be detected. Analysis of primary cells revealed substantial constitutive NF-kappa B-binding activity in blood monocytes, pleural macrophages and alveolar macrophages. The constitutive NF-kappa B appears to be functionally active, since a low level of tumour necrosis factor (TNF) transcript is detectable in monocytes, and this level can be increased by blocking transcript degradation using cycloheximide. The level of constitutive NF-kappa B in these cells is variable and is frequently found to be lower in the more mature macrophages. Constitutive NF-kappa B was not maintained by autocrine action of cytokines TNF, interleukin 6, interleukin 10, granulocyte-macrophage colony-stimulating factor or macrophage colony-stimulating factor, since neutralizing antibodies did not reduce constitutive DNA-binding activity. Furthermore, blockade of prostaglandin or leukotriene biosynthesis did not affect constitutive NF-kappa B.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Constitutive nuclear NF-kappa B in cells of the monocyte lineage. 799 62

To characterize the mechanism by which interleukin 10 (IL-10) inhibits Th1 responses to intracellular pathogens, we evaluated the interaction between IL-10 and Mycobacterium tuberculosis-induced gamma interferon (IFN-gamma) production by peripheral blood mononuclear cells from persons across the spectrum of tuberculous infection. M. tuberculosis-induced IFN-gamma production was highest in healthy tuberculin reactors, intermediate in human immunodeficiency virus (HIV)-negative tuberculosis patients, and lowest in HIV-infected tuberculosis patients. Neutralizing antibodies to IL-10 increased IFN-gamma production in HIV-infected and HIV-negative tuberculosis patients by enhancing monocyte IL-12 production. Expression of the T-cell-costimulatory molecule CTLA-4 was depressed in M. tuberculosis-stimulated peripheral blood mononuclear cells from tuberculosis patients, and anti-IL-10 and Il-12 upregulated expression of CTLA-4. These findings provide evidence that intracellular pathogens can inhibit Th1 responses and downregulate expression of specific costimulatory molecules.
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PMID:Interleukin-10 downregulates Mycobacterium tuberculosis-induced Th1 responses and CTLA-4 expression. 864

We describe a human immunodeficiency virus-negative infant with chronic intractable diarrhea due to Cryptosporidium parvum; he had a history of significant weight loss since the second week of life. A preliminary study of his immune function was negative for primary immunodeficiency. To further study his immune function, proliferation of peripheral blood mononuclear cells (PBMCs) was elicited by crude antigenic extract from C. parvum oocysts (CCE). Supernatants of CCE-stimulated PBMCs contained interleukin 10 but not interferon gamma (IFN-gamma), while PBMCs from a control (a 2-year-old immunocompetent infant who had recovered from cryptosporidiosis) showed a strong response to IFN-gamma when stimulated with CCE. These results stress the role of IFN-gamma in recovery from cryptosporidiosis.
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PMID:Severe, protracted intestinal cryptosporidiosis associated with interferon gamma deficiency: pediatric case report. 895 96

The effects of recombinant gp41 (rgp41) protein of the human immunodeficiency virus type 1 (HIV-1) on interleukin 10 (IL-10) expression and production using human peripheral blood mononuclear cells was investigated. Expression of IL-10 mRNA was demonstrated within 3 h of cell exposure to endotoxin-free rgp41 by RT-PCR and Northern blot analyses in a time- and dose-dependent manner. IL-10 protein was detected in the supernatants of peripheral blood mononuclear cells following stimulation with rgp41 also in a dose dependent manner. Fractionation of peripheral blood mononuclear cells showed that purified monocytes but not purified T-lymphocytes induced expression of IL-10 mRNA by rgp41. Recombinant HIV-1 gp120 exhibits similar influences on the induction of IL-10. These results indicate that both of these components of envelope proteins may play an important role in HIV related immunomodulation by influencing regulatory functions of monocytes and macrophages.
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PMID:HIV-1 recombinant gp41 induces IL-10 expression and production in peripheral blood monocytes but not in T-lymphocytes. 914 42

Concurrent infections in patients with human immunodeficiency virus (HIV) infection stimulate HIV replication. Chemokine receptors CXCR4 and CCR5 can act as HIV coreceptors. The authors hypothesized that concurrent infection increases the HIV load through up-regulation of CXCR4 and CCR5. Using experimental endotoxemia as a model of infection, changes in HIV coreceptor expression were assessed in 8 subjects injected with lipopolysaccharide (LPS, 4 ng/kg). The expression of CXCR4 and CCR5 on CD4(+) T cells was increased 2- to 4-fold, 4 to 6 hours after LPS injection. In whole blood in vitro, LPS induced a time- and dose-dependent increase in the expression of CXCR4 and CCR5 on CD4(+) T cells. Similar changes were observed after stimulation with cell wall components of Mycobacterium tuberculosis (lipoarabinnomannan) or Staphylococcus aureus (lipoteichoic acid), or with staphylococcal enterotoxin B. LPS increased viral infectivity of CD4-enriched peripheral blood mononuclear cells (PBMCs) with a T-tropic HIV strain. In contrast, M-tropic virus infectivity was reduced, possibly because of elevated levels of the CCR5 ligand cytokines RANTES and MIP-1beta. LPS-stimulated up-regulation of CXCR4 and CCR5 in vitro was inhibited by anti-TNF and anti-IFN gamma. Incubation with recombinant TNF or IFN gamma mimicked the LPS effect. Anti-interleukin 10 (anti-IL-10) reduced CCR5 expression, without influencing CXCR4. In accordance, rIL-10 induced up-regulation of CCR5, but not of CXCR4. Intercurrent infections during HIV infection may up-regulate CXCR4 and CCR5 on CD4(+) T cells, at least in part via the action of cytokines. Such infections may favor selectivity of HIV for CD4(+) T cells expressing CXCR4. (Blood. 2000;96:2649-2654)
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PMID:Up-regulation of HIV coreceptors CXCR4 and CCR5 on CD4(+) T cells during human endotoxemia and after stimulation with (myco)bacterial antigens: the role of cytokines. 1102 94

Intracellular expression of several cytokines was assessed in lymphocytes and monocytes of children with transient hypogammaglobulinaemia of infancy (THI) and selective IgA deficiency (SIgAD). THI was characterized by an increased frequency of CD3+/CD4+ lymphocytes expressing tumour necrosis factor alpha (TNF-alpha), TNF-beta and interleukin 10 (IL-10), while in SIgAD elevated numbers of these cells containing TNF-alpha and interferon gamma (IFN-gamma) were observed. No changes in the number of CD4+ T cells expressing IL-4 in both diseases were noted. The proportion of CD33+ monocytes containing TNF-alpha both in THI and SIgAD was unchanged. The secretion of IL-12 by peripheral blood mononuclear cells (PBMCs) of patients with THI and SIgAD was significantly elevated and associated with an increased frequency of IL-12 expressing monocytes in THI but not in SIgAD. IL-18 secretion was slightly, but not significantly, elevated in both diseases. Intracellular Th1 and Th2 type cytokines within CD3+/CD4+ lymphocytes were also determined in the normal blood donors that showed high or low production of IgG and IgA in vitro. In low producers of IgG an increased proportion of CD3+/CD4+ cells expressing TNF-alpha and IFN-gamma was found, while in low IgA responders only elevated TNF-alpha positive CD3+/CD4+ cells were observed. These results suggest that THI and SIgAD may represent diseases with an excessive Th1 type response that is associated with an up-regulation of IL-12 secretion and, at least in THI, elevated numbers of monocytes expressing intracellular IL-12. Up-regulation of IL-12 may be the essential factor in the patomechanism(s) of these diseases as already described in common variable immunodeficiency (CVID).
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PMID:Intracellular cytokine production by Th1/Th2 lymphocytes and monocytes of children with symptomatic transient hypogammaglobulinaemia of infancy (THI) and selective IgA deficiency (SIgAD). 1196 68

Chronic graft-versus-host disease (cGVHD) is characterized by a state of profound immunodeficiency in association with alloreactive and autoimmune phenomena. These observations indicate an impairment of immunologic tolerance that could involve both central and peripheral mechanisms. Defective thymic function may contribute to dysregulation of central tolerance, but few studies have addressed peripheral tolerance. Recently a population of CD4+CD25+ T cells (Treg cells) has been characterized, which controls immunologic reactivity in vivo and which on transfer can prevent experimental acute GVHD. We investigated the number and function of peripheral blood CD4+CD25high T cells in patients more than 100 days after allogeneic hematopoietic stem cell transplantation. Patients with cGVHD had markedly elevated numbers of CD4+CD25high T cells as compared to patients without GVHD. CD4+CD25high T cells derived from patients in both groups were of donor origin, lacked markers of recent activation, and expressed intracellular CD152. In contrast to controls, CD4+CD25high T cells derived from patients with cGVHD were characterized by lower surface CD62L expression. In vitro, CD4+CD25high T cells were hyporesponsive to polyclonal stimulation and suppressed the proliferation and cytokine synthesis of CD4+CD25- cells, an effect that was independent of interleukin 10. These results indicate that chronic graft-versus-host injury does not occur as a result of Treg cell deficiency.
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PMID:Chronic graft-versus-host disease is associated with increased numbers of peripheral blood CD4+CD25high regulatory T cells. 1460 70


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