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)

The expression of Fc epsilon R on human lymphocytes was studied with the anti-Fc epsilon R mAbs. Fc epsilon R was expressed on most mu+,delta+ circulating B cells, whereas T cells did not express Fc epsilon R even in patients with hyper-IgE syndrome. B cells with gamma, alpha, or epsilon phenotype did not express Fc epsilon R, moreover its expression could not be induced, suggesting that the Fc epsilon R expression was correlated with isotype switching. mu+delta+ B cells in bone marrow did not express Fc epsilon R, but PHA-sup (supernatant from PHA-stimulated cell cultures) could induce its expression, and the addition of IgE augmented this induction. Recombinant IL-2, IL-1, IFN-gamma or -beta, or purified B cell differentiation factor (BSF-2 B cell-stimulatory factor 2) could not induce Fc epsilon R expression in bone marrow B cells. IFN-gamma inhibited the Fc epsilon R expression induced by PHA-sup, suggesting that the human counterpart of BSF-1 may be responsible for Fc epsilon R expression in bone marrow B cells. B cells from patients with common variable immunodeficiency and ataxia telangiectasia did not express Fc epsilon R, but PHA-sup could induce its expression, indicating that circulating B cells of these patients are at a differentiation stage similar to B cells in bone marrow. The study showed that Fc epsilon R is a B cell-specific differentiation marker, the expression of which is restricted to a defined stage of B cell differentiation.
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PMID:Fc epsilon receptor, a specific differentiation marker transiently expressed on mature B cells before isotype switching. 294 90

Immunodeficiency syndromes associated with protein-energy malnutrition (PEM) have been documented extensively, although to date the mechanism underlying these defects remains uncharacterized. In this study, we have evaluated T, B, and antigen-presenting cell functions of malnourished mice fed a 4% protein diet compared with litter-mate controls fed a 20% protein diet. Spleen cells from malnourished mice presented both soluble foreign protein and allogeneic MHC antigens less efficiently than control mice. However, T cells from malnourished animals demonstrated effective or enhanced specific T-cell activation when stimulated with allogeneic cells, while B cells from protein-deprived animals responded normally in proliferative responses to T-cell driven cognate and non-cognate, as well as mitogen, stimulation. To assess further antigen-presenting cell function, three requirements for successful antigen presentation were evaluated. First, the proliferation of the IL-1-dependent cloned T-cell line D10 demonstrated a slight deficiency in IL-1 production by malnourished splenic antigen-presenting cells, and the addition of saturating amounts of IL-1 to the assay could partially reconstitute function. Second, quantitative cell-sorter analysis revealed minimal deficiencies of spleen-cell Ia expression. Third, antigen-processing function was assayed in vitro by using processed antigen fragments; no improvement in protein-deprived antigen-presenting function resulted. Together, these findings suggest that either decreased Ia glycoprotein expression on a critical subset of antigen-presenting cells (APCs) or a quantitative deficiency in such a subset of cells, or both, underlie the defective antigen-presenting cell function observed in chronic protein deprivation (CPD).
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PMID:Defective antigen presentation in chronically protein-deprived mice. 313 Mar 10

Interleukin-2 (IL-2) is a chemically defined lymphokine (LK) available as mixed human (LK) preparations, as partially purified lymphoblastoid IL-2, or as recombinant human IL-2. Each has different actions dependent on companion LKs showing synergistic interaction (e.g., IL-1 and gamma-interferon (gamma-IFN]). IL-2 acts to expand activated T cells; to activate natural killer (NK) cells, lymphokine-activated killer (LAK) cells, and cytolytic T cells (CTL); to regulate T-cell ontogeny via actions on prothymocytes and immature T cells; and to induce gamma-IFN and activate tumoricidal macrophages. IL-2 acts via specific cell surface receptors on protein kinase C and cyclic GMP-related mechanisms. While stable, its in vivo half-life is short and its persistence is important for it to induce a response. Toxicities include an influenzia-like syndrome, anemia, eosinophilia, and fluid accumulation. In vivo actions include augmentation of cytotoxic responses at high doses, T-cell adjuvant actions, and T-cell restorative actions at midrange doses and at low doses with companion LKs. Antitumor responses in man and animals occur, but irregularly. They are maximized by the concomitant use of LAK cells, cytoreductive therapy, antisuppressor cell therapy, and regional or persistent administration. IL-2 offers hope for more effective therapy of cancer and a variety of immunodeficiency diseases involving IL-2 defects, including AIDS, viral infections, and autoimmune diseases.
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PMID:Recent advances in the preclinical and clinical immunopharmacology of interleukin-2: emphasis on IL-2 as an immunorestorative agent. 314 Oct 54

Infection of monocyte-macrophages with human immunodeficiency virus may be central to the pathogenesis of the acquired immunodeficiency syndrome. The ability of infected macrophages to prime T cells through IL-1 production was investigated in vitro. Purified human monocytes maintained in suspension culture were infected with strain HIV-DV. Intracellular expression of virus p24 antigen increased from undetectable levels immediately after infection to 13-59% of cells by 10-14 d; infected macrophages remained viable for up to 60 d. Supernatants collected between 14 and 20 d after infection were examined in the murine thymocyte co-mitogenesis assay and demonstrated to contain a potent IL-1 inhibitor, designated contra-IL-1. Contra-IL-1 activity was present in all supernatants examined after 4 d of infection, and peaked coincident with peak p24 antigen expression. Inhibitory activity was not present in uninfected cells. Contra-IL-1 activity eluted after gel filtration with an approximate molecular weight of 9 kD. Inhibitory activity was removed by exposure to heat or acid pH, or by incubation with chymotrypsin or staphylococcal V8 protease. Contra-IL-1 did not inhibit IL-2- or IL-4-dependent proliferation of murine T cell lines. Despite its ability to inhibit IL-1 activity, contra-IL-1 did not interfere with the binding of recombinant IL-1 beta to a fibroblast cell line. Contra-IL-1 inhibited the proliferation of normal peripheral blood mononuclear cells to both concanavalin A and tetanus toxoid; inhibition could be attenuated by the addition of exogenous IL-1. Messenger RNA extracted from infected macrophages was examined by Northern analysis for the presence of message to IL-1 beta. No message was apparent, suggesting that the presence of contra-IL-1 was not obscuring the concomitant release of IL-1. Infected macrophages stimulated with endotoxin generated readily detectable message for IL-1 beta. Spleen macrophages purified from two patients with AIDS complicated by immune thrombocytopenia spontaneously expressed p24 antigen in vitro and released contra-IL-1 activity into the media. Contra-IL-1 may contribute to the immune dysfunction of AIDS.
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PMID:Release of interleukin 1 inhibitory activity (contra-IL-1) by human monocyte-derived macrophages infected with human immunodeficiency virus in vitro and in vivo. 326 91

Monocytes in a familial monocyte disorder, a recently recognized primary immunodeficiency syndrome, with impaired phagocytic functions were studied for their ability to produce interleukin 1 (IL-1) as well as the surface property. Monocytes from two children (siblings) with the disorder possessed CD11b, CD13, CD14, CD33, Ia and LFA-1/Mac-1/p150,95 beta subunit antigens as determined by flow cytometry. Electron microscopic cytochemistry showed that the monocytes had surface glycoproteins reactive with four representative lectins. The IL-1 production by monocytes was assayed in the two patients and compared with that in six children with primary immunodeficiency syndromes and some monocyte abnormalities; three had congenital neutropenia, two had hyper-IgE syndrome, and one had defective monocyte chemotaxis. Monocyte culture supernatants were prepared with stimulation by lipopolysaccharide or silica, and their IL-1 activity was measured by the mouse thymocyte-proliferation assay. The patients' monocytes were defective in IL-1 production: the values were less than 1.0% of the control monocyte values (n = 12) and were in contrast with those of congenital neutropenia monocytes of 186.2% to 204.3%. These results demonstrate a familial monocyte disorder which is characteristic among the immunodeficiency syndromes with regard to the defective IL-1 production and the impaired phagocytic functions.
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PMID:Defective interleukin-1 production in a familial monocyte disorder with a combined abnormality of mobility and phagocytosis-killing. 326 74

Monocyte functions, including interleukin 1 (IL-1) production, have been shown previously to be impaired in acquired immunodeficiency syndrome (AIDS). We have fractionated culture supernatants from unstimulated peripheral blood mononuclear cells (PBMCs) to determine whether the low IL-1 activity in AIDS was due to the presence of IL-1 inhibitors. The results demonstrate that PBMCs from patients with AIDS produce increased amounts of IL-1 activity compared with those of controls together with marked increases (10- to 20-fold) in the amounts of 50,000-100,000 and 6000-9000 molecular weight (MW) factors which inhibit IL-1 activity. These inhibitors mask IL-1 activity measured in the standard thymocyte proliferation assay for IL-1. The 6000-9000 MW IL-1 inhibitor shows the greatest increase in all AIDS patients (n = 5) compared with that of controls (n = 7). This inhibitor may block the IL-1 dependent maturation of T lymphocytes in AIDS and thereby contribute to the immunodeficiency.
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PMID:Interleukin 1 inhibitor masks high interleukin 1 production in acquired immunodeficiency syndrome (AIDS). 349 12

In recent studies from this laboratory, the immunologic properties of a new class of activator, the C8-derivatized guanine ribonucleosides have been described. These agents are potent lymphocyte activators which appear to gain access to the interior of the cell by the purine nucleoside facilitated transport mechanism and to activate the cell at an intracellular triggering site. Cyclic GMP does not appear to be a direct or indirect mediator of these events. The major lymphocyte population responsive to these compounds appears to be a mature group of B lymphocytes with a minor contribution provided by a subpopulation of less mature B cells. These nucleoside analogues exert a variety of pleiotropic effects, including polyclonal activation of B cells to secrete immunoglobulin, immunoenhancement of thymus-dependent and thymus-independent immune responses, induction of interleukin 1-like activity in cultured macrophages, and transmission of T cell-like inductive signals to B cells. This T cell-replacing activity appears to be T cell-independent and interleukin-2 independent, but is capable of synergizing with both T cells and T cell-derived lymphokines. Moreover, the T cell-like signals provided by the C8-derivatized nucleosides appear to be independent of the first signals (leading to clonal expansion) provided by these agents, in that antigen alone is able to provide a perfectly satisfactory inductive signal for B cells. Studies to date suggest that these nucleoside derivatives are capable of ameliorating immune deficits in serveral different models of murine immunodeficiency.
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PMID:Immunobiologic properties of the C8-derivatized guanine ribonucleosides. 660 52

Studies were designed to investigate whether the cellular immunodeficiency state observed in human glioblastoma patients could be due to inhibitory factors released by the tumor cells. Cultured human glioblastoma cells were found to secrete an interleukin 1-like factor (m.w. 22,000) and a factor (m.w. 97,000) that inhibits interleukin 2 (IL 2)-dependent T cell mechanisms. This is demonstrated by its inhibitory effect on the IL 2-induced proliferation of T cell clones and on the induction of alloreactive cytotoxic T cells in mixed lymphocyte cultures. Additionally the glioblastoma cell-derived 97,000-m.w. factor inhibited growth of neuroblasts but not of fibroblasts and thus shares the characteristics of the neuroblast growth inhibition factor (NGIF) previously detected in the supernatant of fetal rat glia cell cultures. If released by glioblastoma cells in vivo, the factor may contribute to impaired immunosurveillance and to the cellular immunodeficiency state detected in the patients.
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PMID:Glioblastoma cells release interleukin 1 and factors inhibiting interleukin 2-mediated effects. 660 49

The cellular immune defect in untreated Hodgkin's disease (HD) has long been recognized. This defect appears to be responsible for at least some of the morbidity and ultimately the mortality associated with the disease. In recent years, many studies have shown that the T cell component of the immune response is the apparent site where the defect in HD exists and where the immunoregulatory abnormalities that may account for the deficit are observed. The discovery of the lymphokines and monokines, comprising the human interleukin system, has elucidated some aspects of the regulatory control of the functional pathways involved in T lymphocyte activation and proliferation. The interleukin system can therefore provide the framework to dissect immunodeficiency states, such as that seen in HD. The present study indicates that HD patients' interleukin 1 (IL1) response appears to be normal, as is their T cell proliferative response to exogenous IL2. Interleukin 2 production by HD patients' peripheral blood mononuclear cells, however, is decreased when compared with age/sex-matched controls. The inability to generate IL2 after appropriate stimulation may reflect either a primary cellular defect or a regulatory defect, such as excessive immunosuppression, giving rise to the characteristic T cell hyporesponsiveness seen in HD.
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PMID:Association of an interleukin abnormality with the T cell defect in Hodgkin's disease. 661 Nov 80

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


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