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

The ability of the human immunodeficiency virus (HIV) to replicate in CD+ T lymphocytes and mononuclear phagocytes(MP) is strongly influenced by immunoregulatory cytokines. In the T cell system, interleukin-2 (IL-2) provides a mitogenic signal leading to both cell proliferation and virus replication. Among other HIV-inductive cytokines, only tumor necrosis factor-alpha or -beta (TNF-alpha/-beta) have been shown thus far to trigger virus expression both in T cells and MP. The mechanism of action of TNF involves the activation of the cellular transcription factor NF-kB which binds to specific consensus sequences present in the enhancer region of the HIV proviral LTR. In addition, several other cytokines (including colony stimulating factors, IL-1, IL-3, and IL-6) have demonstrated upregulatory effects on HIV production in MP, whereas nonimmune interferons (INF-alpha/-beta) have been shown to suppress HIV replication in T cells and MP by acting at different phases in the virus life cycle. Finally, cytokines such as TGF-beta, IFN-gamma, and IL-4 have demonstrated either upregulatory or suppressive effects on virus expression depending on the experimental conditions. This scenario indicates that HIV expression is under the control of a complex network of immunoregulatory cytokines, in addition to its own endogenous regulatory proteins, suggesting that new pharmacologic strategies may be aimed at either mimicking or interrupting cytokine-dependent virus expression. In this regard, a number of different physiologic and pharmacologic agents capable of interfering with cytokine-mediated events, including glucocorticoids, anti-oxidants, such as N-Acetyl-L-Cysteine (NAC), and retinoic acid (RA) have already been shown to profoundly affect HIV replication in vitro.
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PMID:The effect of cytokines and pharmacologic agents on chronic HIV infection. 154 Apr 7

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

Simian immunodeficiency viruses (SIV) are a family of primate lentiviruses similar to human immunodeficiency viruses (HIV) in their genetic sequence and pathogenesis. However, host-derived cofactors which may determine the extent of viral replication are not clearly defined for SIV or HIV infections. A HuT-78 cell line chronically infected with SIV/mac strain 251, was biologically cloned and characterized for the ability to produce infectious viral particles, viral structural protein profile, cellular antigen surface phenotype and tested to determine the effects of recombinant cytokines on SIV replication. Reverse transcriptase (RT) assay was used to measure the replication of SIV/mac in response to various concentrations of recombinant cytokines (1-1000 units/ml). We report that tumor necrosis factor-alpha (rTNF-alpha), gamma-interferon (rIFN-gamma), interleukin 2 (rIL-2), and granulocyte-macrophage colony stimulating factor (rGM-CSF) induced approximately a 2 to 3 fold increase in virus RT activity compared with untreated SIV-infected HuT-78 cells. In contrast, viral replication was not enhanced or minimally enhanced by interleukin 1 (rIL-1), interleukin 3 (rIL-3), or interleukin 4 (rIL-4) at similar dosages. Furthermore, SIV replication in response to rTNF-alpha and rIFN-gamma occurred in a dose dependent fashion. These data suggest that SIV-infected T-lymphocyte lines are responsive to particular cytokines resulting in increased virus production.
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PMID:Cytokine enhancement of simian immunodeficiency virus (SIV/mac) from a chronically infected cloned T-cell line (HuT-78). 172 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

We showed that an extract (PC6) from cones of Pinus parviflora Sieb et Zucc induced the human T-cell line CEM to produce a pepsin-sensitive soluble factor(s) that could inhibit the replication of the type 1 human immunodeficiency virus (HIV-1) in CEM T cells, in U-937 histocytes, in THP-1 monocytes, and in mitogen-activated human tonsillar mononuclear cells. Indirect immunofluorescence staining and polymerase chain reaction analysis of the PC6-induced CEM cells revealed the absence of known lymphokines/cytokines except granulocyte/macrophage colony-stimulating factor (GM-CSF), interleukin 3 (IL-3), transforming growth factor beta 1 (TGF-beta 1), and tumor necrosis factor alpha (TNF-alpha). However, functional studies with recombinant IL-3, TNF-alpha, and TGF-beta 1 showed that these three factors did not inhibit HIV-1 replication in CEM cells. Neutralization of the PC6-induced HIV-1-inhibiting factor(s) with commercially available neutralizing antibodies to GM-CSF and TNF-alpha also did not abrogate the anti-HIV-1 impact. Thus, the anti-HIV-1 factor induced by PC6 may be novel. Molecular sieve separation showed that the anti-HIV-1 factor(s) is smaller than 30 kDa. Affinity chromatography using a DEAE-cellulose column enriched the factor that inhibited HIV-1.
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PMID:A soluble factor induced by an extract from Pinus parviflora Sieb et Zucc can inhibit the replication of human immunodeficiency virus in vitro. 200 64

Myelosuppression is a major symptom in the acquired immunodeficiency syndrome (AIDS). Moreover zidovudine, an anti-retroviral drug used to treat AIDS patients has myelosuppressive side effects. Therefore treatment with IL-3, a multi-lineage hemopoietic growth factor may be beneficial for zidovudine-treated individuals. In this study we examined the effect of IL-3 on human immunodeficiency virus (HIV) expression. The proliferative response to rIL-3 and the effects on the replication of the monocytotropic HIV variant, HTLV-III Ba-L, in the absence or presence of the anti-retroviral drug zidovudine was studied in purified human peripheral blood monocytes. Zidovudine concentrations sufficient for complete inhibition of HIV replication did not affect rIL-3 induced monocyte proliferation. Although rIL-3, like rGM-CSF, was able to augment HIV expression in monocytes, it did not interfere with the anti-retroviral activity of zidovudine. These data indicate that rIL-3 is a potential candidate for use in myelosupportive therapy in AIDS patients treated with anti-retroviral drugs.
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PMID:Induction of monocyte proliferation and HIV expression by IL-3 does not interfere with anti-viral activity of zidovudine. 220 24

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

As an attempt to elucidate the pathogenesis of human immunodeficiency virus type 1 (HIV-1)-related cytopenia, the effects of infection of long-term primary bone marrow culture (LTBMC)-derived adherent cells on hematopoiesis were investigated. Productive infection could then be established only when using monocytotropic strains HIV-1Ba-L, HIV-1Ada, and HIV-1JR-FL but not with lymphocytotropic strain HIV-1LAI. Culture supernatants were tested for major cytokines involved in the regulation of hematopoiesis: neither IL-3 nor GM-CSF were detectable in the infected or noninfected cultures; in contrast, TGF-beta, TNF-alpha, MIP-1 alpha, Steel Factor, and IL-6 were detected at all times in established LTBMCs, but their levels were not consistently altered by virus replication. In vitro functional analysis by colony and long-term culture assays showed that HIV-1 infection failed to alter either the kinetics or the number of hematopoietic progenitors produced by the stromal layers; it did not interfere with the clonogenicity of exogeneous CD34+ cells in semisolid assays, and no difference was observed relative to the controls when HIV-1-infected stromal layers were tested for their ability to sustain long-term hematopoiesis. These results show that productive and sustained virus replication in the macrophage component of LTBMCs does not significantly alter the profile of major cytokines involved in regulating hematopoiesis, nor is it sufficient by itself for altering in vitro hematopoiesis under the baseline conditions used.
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PMID:In vitro infection of bone marrow-adherent cells by human immunodeficiency virus type 1 (HIV-1) does not alter their ability to support hematopoiesis. 748 69

In this study, we evaluated the effect of a short-term exposure (2 hours) to two different lymphocytotropic strains of human immunodeficiency virus type 1 (HIV-1; HIVIIIB and ICR-3) on the survival of a factor-dependent CD34+ hematopoietic progenitor cell line (TF-1). At flow cytometry analysis, a significant (P < .05) increase in the frequency of apoptotic cell death was observed in HIV-1-treated TF-1 cells, supplemented with low doses of either interleukin-3 (IL-3; 0.02 to 1 ng/mL) or granulocyte-macrophage colony-stimulating factor (GM-CSF; 0.02 to 0.2 ng/mL) with respect to mock-treated cells. On the other hand, higher doses of both cytokines or combinations of suboptimal concentrations of IL-3 plus GM-CSF (eg, 0.2, plus 0.2 ng/mL) completely reversed the HIV-1-induced increase of apoptosis. Remarkably, no signs of productive or latent virus replication were ever observed in HIV-1-treated TF-1 cells up to 16 days of liquid culture. In parallel experiments, the in vitro exposure to HIVIIIB induced a significant and progressive increase of apoptotic death in purified bone marrow CD34+ cells, seeded in liquid cultures in the presence of 1 ng/mL IL-3. The HIV-1-induced apoptosis of TF-1 cells was likely triggered by the simple interaction of HIV-1 envelope glycoprotein gp120 with CD4 receptor, which was expressed at a low level on the surface of TF-1 cells. In fact, treatment of TF-1 cells with recombinant gp120 plus a polyclonal anti-gp120 antibody or with anti-CD4 monoclonal antibody plus rabbit antimouse IgG significantly increased the percentage of apoptotic death. These data suggest that HIV-1, and perhaps also free gp120 in the presence of anti-gp120 antibody; could play a direct role in the pathogenesis of peripheral blood cytopenias in acquired immunodeficiency syndrome patients by inducing apoptotic death of hematopoietic progenitor cells without the need of a direct infection.
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PMID:In vitro exposure to human immunodeficiency virus type 1 induces apoptotic cell death of the factor-dependent TF-1 hematopoietic cell line. 750 78


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