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)

Peyer's patch (PP) T cells through the production of appropriate cytokines foster the development of immunity to the intestinal protozoan parasites such as Giardia. T cell destruction by the human immunodeficiency virus precedes the development of acquired immune deficiency syndrome. Thus, HIV may increase susceptibility to intestinal parasite infections. Therefore, we measured the resistance and T cell cytokine responses to Giardia in C57B1/6 mice infected with the retrovirus LP-BM5 which produces a murine AIDS (MAIDS). Mice with MAIDS and controls were intragastrically challenged with 1 x 10(5) G. muris cysts. Fecal counts were measured weekly following challenge. Also, PP T cell production of interleukin (IL)2, IL3, IL4, and Interferon-gamma in response to G. muris trophozoite antigens displayed on antigen presenting cells were measured at these times. Prior to day 14 of the infection, the number of Giardia cysts in the retrovirus group paralleled that in controls. However, by day 21 after Giardia infection, mice with MAIDS failed to clear the Giardia cysts from the intestine while the control mice were completely free of cysts. IL2 and IL4 production in response to Giardia trophozoites by unfractionated PP lymphocytes were severely depressed in the retrovirus infected group, while IFN-gamma production was increased. Depressed cytokine production was most likely due to depressed PP T cell numbers. When fractionated enriched T cells were adjusted to a uniform concentration in in vitro immunization cultures, the production of IL2 and IL4/IL5 were similar between retrovirus infected compared with control mice. Recoverable PP T cells were lower in mice with MAIDS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Suppression of resistance to Giardia muris and cytokine production in a murine model of acquired immune deficiency syndrome. 129 11

Patients infected with the human immunodeficiency virus are at increased risk for developing intermediate-grade and high-grade B-cell lymphomas that in many instances contain Epstein-Barr viral (EBV) DNA. Because interleukin-5 (IL-5), a potent stimulator of eosinophil growth and differentiation, has been detected recently in EBV-infected B-cells, we hypothesized that some acquired immunodeficiency syndrome-related lymphomas with EBV DNA also might contain eosinophilia and IL-5. After reviewing files entered into our archives during the past 3 years, we identified four cases of human immunodeficiency virus-associated, high-grade, B-cell lymphomas that also contained extensive infiltration by eosinophils. Cryopreserved DNA from two of these four cases was available for amplification by the polymerase chain reaction, and both cases yielded an easily identifiable, EBV-specific amplification product. From one of these cases we also were able to extract mRNA and perform messenger amplification phenotyping (MAPPING) for the detection of mRNA coding for IL-5. After reverse transcription of mRNA from this case to cDNA and amplification by the polymerase chain reaction, we identified an amplification product that co-migrated with IL-5-positive controls in an agarose gel. We conclude that some AIDS-related lymphomas are associated with eosinophilia and that the eosinophilia may be related to EBV infection and transcriptional activation of the IL-5 gene.
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PMID:Epstein-Barr virus and interleukin-5 mRNA in acquired immunodeficiency syndrome-related lymphomas with eosinophilia. 133 44

Progressive lymphoproliferation and increasingly severe immunodeficiency are prominent features of a syndrome, designated mouse AIDS, which develops in susceptible strains of mice infected with the mixture of murine leukemia viruses, termed LP-BM5. Development of splenomegaly and lymphadenopathy, caused primarily by increases in B cell immunoblasts, requires the presence of CD4+ T cells and is assumed to be mediated by lymphokines produced by these cells inasmuch as progression of disease is markedly inhibited by treatment of infected mice with cyclosporin A. Studies of spleen cells from infected mice revealed spontaneous production of cytokines (IFN-gamma, IL-2, IL-4, IL-5, and IL-10) characteristic of Th0 (or a mixture of Th1 and Th2) T helper cells at 1 wk after infection. At later times, IFN-gamma and IL-2, characteristic products of Th1 helper clones, were expressed poorly, either spontaneously or after stimulation of cells with Con A. In contrast, IL-4, IL-5, IL-6, and IL-10, cytokines typically synthesized by Th2 cells, were produced in response to Con A or spontaneously through 18 wk post-infection. Increased serum IgE levels and enhanced IL-10 mRNA expression were consistent with expression of Th2 cytokines at biologically significant levels in vivo. Selective depletion of T cell subsets before stimulation with Con A showed that CD4+ T cells were the primary source of IL-2, IL-4, IL-10, and, to a lesser extent, IFN-gamma in spleens and lymph nodes of normal or infected mice. These results suggest that persistent activation of CD4+ T cells with the lymphokine profile of Th2 helper clones is responsible for chronic B cell stimulation, down-regulation of Th1 cytokines, and impaired CD8+ T cell function in mouse AIDS. This provides the first demonstration that, like many parasitic infections, viruses encoding potent antigenic stimuli can markedly affect the balance of Th subset expression.
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PMID:CD4+ subset regulation in viral infection. Preferential activation of Th2 cells during progression of retrovirus-induced immunodeficiency in mice. 134 85

A syndrome characterized by severe immunodeficiency and lymphoproliferation develops in susceptible strains of mice infected with a mixture of murine leukemia viruses (MuLVs) designated LP-BM5 MuLV. The etiologic agent in this mixture has been shown to be a replication-defective virus (BM5d) with a 4.8-kb genome that required replication-competent helper viruses, primarily ecotropic (BM5e), for cell-to-cell spread in the host. In the present study, we studied the expression of BM5d and BM5e in tissues of infected mice at various times after inoculation in relation to the expression of cytokine genes that may contribute to the pathogenesis of this disorder. Northern (RNA) analysis of total RNA showed that BM5d was expressed at significant levels in lymphoid tissues within 1 week of infection and that the levels of expression increased with time after inoculation. By 16 weeks postinfection, BM5d was expressed in all tissues examined. Expression of BM5e was relatively more restricted to lymphoid tissues and was detected at lower levels than expression of BM5d at early times after infection, but this virus was expressed in all tissues by 16 weeks. Infection with the virus mixture was associated with constitutive expression of tumor necrosis factor in all tissues examined and of interleukin-1 (IL-1) in lymphoid tissues within 1 week of infection, and at later times with widespread expression of these cytokines and gamma interferon. Also, the levels of interferon regulatory factor 1 mRNA were significantly increased in all infected tissues during the infection. In contrast, expression of IL-3, IL-4, IL-5, and IL-6 was not detectable by Northern analysis of the respective mRNAs in any infected tissue at early or late times postinfection.
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PMID:Expression of defective virus and cytokine genes in murine AIDS. 170 43

Normal human bone marrow, cultured in vitro with interleukin 5 to promote eosinophil production and maturation, was inoculated with cell-free isolates of human immunodeficiency virus type 1 (HIV-1). CD4 expression by eosinophil precursors, determined by immunocytochemistry, was found to be greatest early in their maturation with a rapid decline after 28 d in culture. Productive HIV infection of eosinophil precursors was detected 14 d after inoculation, by a combination of immunostaining for HIV-1 p24 and gp41/160 and in situ hybridization for viral RNA, together with assay of culture supernatants for p24 antigen and reverse transcriptase activity. Thus, eosinophils are susceptible to productive HIV-1 infection in vitro and may be an important reservoir for the virus in vivo.
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PMID:Human immunodeficiency virus infection of eosinophils in human bone marrow cultures. 174 91

A 4-year-old female with severe combined immunodeficiency (SCID) had normal numbers of T cells in circulation and normal T cell subsets. However, her T cells proliferated poorly to mitogens and did not proliferate to antigens or to anti-CD3 mAb. Interleukin-2 (IL-2) receptor expression was normal but IL-2 synthesis was undetectable. The addition of recombinant IL-2 to a mitogen-stimulated culture resulted in normalization of the proliferative response. Northern blot analysis of total RNA derived from the patient's T cells revealed a weak or absent expression of mRNA coding for IL-2, IL-3, IL-4, and IL-5. In contrast, there were normal amounts of mRNA coding for granulocyte-macrophage colony-stimulating factor (GM-CSF). Tumor necrosis factor and IL-6 production was also normal. Nuclear run on transcriptional assays revealed markedly decreased levels of newly initiated nuclear transcripts coding for IL-2, IL-3, IL-4, and IL-5 and normal levels of GM-CSF transcripts in patient relative to control lymphocytes. These results indicate that the patient's T cells suffered from a defect affecting the transcription of multiple T cell lymphokines and suggest that abnormalities affecting the production of T cell lymphokines may underlie some of the primary immunodeficiency diseases.
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PMID:Novel immune deficiencies: defective transcription of lymphokine genes. 193 9

Interleukin-5 (IL-5) has previously been demonstrated to enhance immunoglobulin synthesis, especially IgA. Thus, it could be hypothesized that a defect production of IL-5 may cause immunoglobulin deficiency. We have analysed the frequency of IL-5 mRNA-producing cells in healthy adults and in patients with common variable immunodeficiency or selective IgA deficiency. Unstimulated lymphocytes were rarely found to synthesize IL-5 as measured by in situ hybridization. However, pokeweed mitogen and several other activating ligands induced the synthesis of IL-5 mRNA in peripheral blood and spleen lymphocyte cultures. After pokeweed mitogen activation, the number of IL-5 mRNA-producing cells most often peaked on day 3 with a maximal frequency of around 1-2% of mononuclear cells. In a kinetic study we were unable to detect any peak frequency differences between healthy controls (mean 0.44%) and 20 patients (mean 0.58%). Thus, although IL-5 has been reported to be an important regulator of IgA synthesis, a defect production does not seem to be the underlying mechanism in human immunoglobulin deficiency.
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PMID:Frequencies of interleukin-5 mRNA-producing cells in healthy individuals and in immunoglobulin-deficient patients, measured by in situ hybridization. 239 11

We report a 3 1/2-week-old male infant with Down's syndrome who presented with abdominal distention, ascites, and eosinophilia and was subsequently diagnosed as having an abdominal non-Hodgkin's lymphoma of T-cell type. Because of the unusual association of these two conditions, especially at this early age, the literature was reviewed regarding the possible oncogenic mechanisms in Down's syndrome patients and the various malignancies associated with this condition. Non-Hodgkin's lymphoma is discussed briefly with emphasis on its possible etiologic mechanisms and predisposing conditions, especially the immunodeficiency states. Because this infant presented with non-Hodgkin's lymphoma at an early age, it is considered unlikely that an immunoaberration is responsible. Also, a short discussion of this patient's peripheral and bone marrow eosinophilia is given, implicating a T-cell product (e.g., eosinophil differentiation factor) as the putative pathophysiologic mechanism.
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PMID:Non-Hodgkin's lymphoma in a neonate with Down's syndrome. Case report and literature review. 252 4

Figure 1 depicts some of the potential interactions of the interleukins. Among the substances discussed here, only IL-2 has been used to any large degree in a clinical series. Other cytokines not discussed including some of the colony stimulating factors, tumor necrosis factor and the interferons have also been used in clinical trials. Undoubtedly as we learn more about interleukins IL-1 through IL-7, clinical applications will become apparent. For the allergist/immunologist there are two areas of greatest potential interest. The first of these is in treating immunodeficiency states. Preliminary studies of the use of IL-2 in patients with T cell dysfunction suggest that this substance may be useful in treating selective T cell disorders. IL-4, 5, and 6 all have some influence on B cell function. It is likely that in the near future one or more of these agents will be used clinically. It is also clear that the interleukins have the potential to influence basic mechanisms known to be important in allergic disease. IL-3 is the major factor influencing mast cell growth. IL-4 among other things, promotes B cells to switch to IgE synthesis as well as to induce Fc epsilon RII receptors on B cells. IL-5 is important in the differentiation and growth of eosinophils. Finally, IL-6 is the terminal differentiation factor that causes B cells to become plasma cells. The next few years should result in an even better understanding of the role of each of these interleukins. It is likely that such information will greatly expand the horizons for understanding the pathogenesis of many immunologically mediated diseases and will provide the basis for new modalities of treatment.
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PMID:Interleukins in immunologic and allergic diseases. 267 43

A toddler with common variable hypoimmunoglobulinemia (CVH), inflammatory bowel disease, and recurrent Pneumocystis carinii pneumonia (PCP) on intravenous gammaglobulin (IVIG) replacement was evaluated for a combined cellular immunodeficiency. He had a normal number of circulating T-cells, natural killer (NK) cells, T-cell subset percentages, and his peripheral blood mononuclear (PBM)-derived B-cell number was low. PBM mitogen blastogenesis and mixed lymphocyte reaction (MLR) were normal. MLR activated T-cells expressed class I and II MHC antigens, interleukin 2 (IL-2), and B-cell growth factor (IL-5)-related receptors. The patient's T-cells induced control B-cell maturation with pokeweed mitogen (PWM-PC), and did not suppress PWM-PC production by allogeneic PBM. Bone marrow (BM) CD19+ B-cell number varied between 10 and 44% of all PBM, and the BM B-cell-enriched fraction failed to differentiate to PWM-PC with autologous or allogeneic T-cell help. The NK activity assayed using K562 target cells was deficient, 9.2 x 7.7% (6.9-9.2%) pt, control 35.9 x 35.8% (16.3-67.2% +/- 12.8). In the presence of interferon-alpha, 800 U/ml, the patient's NK activity increased to 17.2 x 14.9% (12.6-17.2%), control 35.9 x 51.0% (36.5-72.3% +/- 12.0). The patient's cell-mediated lympholysis of HLA nonidentical, allogeneic stimulators was normal. Maintaining trough serum IgG levels above 500 mg/dl was required to suppress recurrent PCP. This functional NK deficiency may be relevant to the development of recurrent PCP in IVIG-treated CVH patients.
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PMID:Common variable hypogammaglobulinemia, recurrent Pneumocystis carinii pneumonia on intravenous gamma-globulin therapy, and natural killer deficiency. 278 54


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