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)

We have examined the effect and potential mechanism of Cyclosporin A (CsA) on the Interleukin-2-receptor alpha chain (IL-2R alpha) expression in human T-lymphocytes. CsA pretreatment of PHA-activated T-cells led to 30-50% decrease in Tac antigen surface expression and a concomitant decrease in the steady state IL-2R alpha mRNA levels. Transacting factors which recognize a kB-like sequence present in the IL-2R alpha chain regulatory region have been suggested to participate in the transcriptional regulation of the IL-2R alpha gene. Using oligonucleotides corresponding to the 5' regulatory region of the IL-2R alpha gene (i.e. 245 to 291 bp upstream of the start codon) and nuclear extract from resting T lymphocytes, we detected two specific bands by gel mobility shift assay. One of these bands is specifically increased after stimulation with phytohemagglutinin (PHA) and it is inhibited by CsA pretreatment. The same pattern of binding activity has been observed with the tandem repeat of NF-kB binding site present in the enhancer element of the human immunodeficiency virus long terminal repeat (HIV-1 LTR). These data suggest that CsA affects IL-2R receptor alpha chain expression by inhibiting the interaction of transacting factors to kB-like sequences after PHA activation. These findings may be of some relevance for the understanding of the immunosuppressive effects of CsA in normal human T lymphocytes.
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PMID:Cyclosporin A inhibits induction of IL-2 receptor alpha chain expression by affecting activation of NF-kB-like factor(s) in cultured human T lymphocytes. 212 97

A peptide sequence in the transmembrane protein of visna virus has been identified that bears a high degree of similarity to a sequence within the transmembrane protein gp41 of human immunodeficiency virus that we have previously shown to be immunosuppressive. Also within the Q (vif/sor) open reading frame of the visna virus genome is a sequence that is highly similar to the immunosuppressive sequence from the retroviral transmembrane protein p15E. We synthesized peptides containing these visna virus sequences and tested them for immunosuppressive activity, comparing them with their human immunodeficiency virus and leukemia retrovirus counterparts. Both the Q- and transmembrane-derived visna virus peptides inhibited lymphoproliferation stimulated by either interleukin-2 or the T-cell antigen receptor in a dose-dependent and sequence-specific manner. The two visna virus peptides also inhibited the enzymatic activity of protein kinase C, thus providing a possible molecular mechanism by which they inhibit immune function.
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PMID:Inhibition of lymphoproliferation and protein kinase C by synthetic peptides with sequence identity to the transmembrane and Q proteins of visna virus. 215 78

Zidovudine (3'-azido-3'-deoxythymidine; AZT) inhibited replication of an immunodeficiency-inducing strain of feline leukemia virus (FeLV-FAIDS) in vitro at concentrations of 0.5-0.005 micrograms/ml. A 25-30% additional antiviral effect was achieved in vitro when AZT was combined with human recombinant alpha interferon 2a (IFN alpha). Oral administration of AZT (20 mg/kg three times daily) to cats resulted in plasma concentrations of 3 micrograms/ml at 2 h post-administration with a T1/2 of approximately 1.60 h. Administration of AZT alone or in combination with IFN alpha or interleukin-2 (IL-2) throughout a 6-week treatment period enabled cats to resist challenge with FeLV-FAIDS. In contrast, those cats treated with IFN alpha or IL-2 alone became persistently antigenemic (core protein p27) in parallel with placebo-treated controls. Antigenemia remained undetectable in AZT-treated cats throughout an 80-day period post-inoculation (38 days after treatment was withdrawn). However, latent FeLV-FAIDS in bone marrow was detectable by in vitro culture of progenitor cells in the presence of hydrocortisone. Serial analysis of circulating p27 antigen, neutralizing antibody, and quantification of latent, reactivatable virus indicated that those animals receiving AZT in combination with IFN alpha were most able to resist FeLV-FAIDS challenge. This work provides additional evidence that early presymptomatic treatment employing combination chemoimmunotherapy can be effective in medical intervention of retroviral infection.
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PMID:Zidovudine in combination with alpha interferon and interleukin-2 as prophylactic therapy for FeLV-induced immunodeficiency syndrome (FeLV-FAIDS). 216 83

The protective immune response to human immunodeficiency virus type 1 (HIV-1) induced by vaccination will likely include cellular immune responses. We measured lymphoproliferative responses in persons vaccinated with a baculovirus-derived recombinant gp160 candidate AIDS vaccine. Twelve volunteers received either 40 micrograms of rgp160, 80 micrograms of rgp160, hepatitis B vaccine, or alum adjuvant alone on days 0, 30, and 180. Peripheral blood lymphocytes were collected on days 0, 28, 60, 120, 210, and 270 and were cryopreserved. Lymphocyte proliferation to mitogens and rgp160 with and without interleukin-2 stimulation were determined, and lymphokine production and antibody synthesis were measured. All vaccinees responded normally to stimulation with phytohemagglutinin and concanavalin A. One of 3 vaccinees who received 40 micrograms of rgp160, 2 of 2 vaccinees who received 80 micrograms of rgp160, and no controls developed rgp160-specific lymphoproliferative responses. No differences in the production of lymphokines (interleukin-2 and interferon-gamma) after stimulation with mitogens or rgp160 were found when rgp160 vaccinees and controls were compared. We conclude that rgp160 candidate vaccine induces antigen-specific lymphoproliferative responses in humans and does not interfere with immunocompetence as measured by in vitro responses to mitogen stimulation.
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PMID:Lymphoproliferative responses to mitogens and HIV-1 envelope glycoprotein among volunteers vaccinated with recombinant gp160. 218 3

Cyclosporin A (CsA) is thought to exert its immunosuppressive effects by inhibiting the expression of a distinct set of lymphokine genes which are induced upon T-cell activation, among them the gene coding for interleukin-2. In addition, the activation of the human immunodeficiency virus (HIV) is partially suppressed. To better understand the molecular mechanisms underlying suppression by CsA, we have investigated the effects of this drug on transcription factors in T cells. Here we report that the formation of two distinct mitogen-inducible DNA-binding complexes, the kappa B complex within the HIV enhancer and the NFAT-1 complex within the interleukin-2 enhancer, is inhibited in the presence of CsA. The kappa B-binding activity with the HIV enhancer is inhibited only if it is activated via the mitogen phytohemagglutinin whereas phorbol myristate acetate-mediated activation is completely insensitive to the drug. This suggests a model in which functionally indistinguishable kappa B complexes can be activated via two separate pathways of signal transduction distinguishable by CsA.
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PMID:Inducible nuclear factor binding to the kappa B elements of the human immunodeficiency virus enhancer in T cells can be blocked by cyclosporin A in a signal-dependent manner. 219 87

Proliferative responses to mitogens were determined by using peripheral blood mononuclear cells from women with active trichomoniasis, with serological evidence of past infection with Trichomonas vaginalis, and with no evidence of current or past infection. Even after the human immunodeficiency virus antibody status of the patients was taken into account, cells from women with active trichomoniasis showed reduced responses to phytohemagglutinin, concanavalin A, pokeweed mitogen, and bacterial lipopolysaccharide. Similar findings were obtained by using spleen cells from mice inoculated subcutaneously with live trichomonads. Reduction in proliferative responses by these cells could be detected 3 days after inoculation. There was some evidence to suggest that more-pathogenic strains of the parasite induced a greater degree of immunosuppression. The responses of spleen cells from mice inoculated with trichomonad-free culture supernatants were within normal limits, indicating that live trichomonads were needed to induce suppression. Support for this was gained from studies with cells from women who were treated successfully. Cells from these women rapidly regained normal lymphoproliferative function. Interleukin-2 (IL-2) production by spleen cells from infected mice was determined from measurements of mitochondrial activity in an IL-2-dependent T-cell line following incubation with stimulated spleen cell culture supernatants. These tests demonstrated lower IL-2 activity in supernatants from cell cultures from infected mice than in those from uninfected mice. The reduction in IL-2 activity did not, however, appear to correlate with the degree of reduction of mitogen-induced lymphoproliferation. Suppression of T-cell-mediated immunity may be one of the mechanisms by which T. vaginalis is able to evade host responses to infection.
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PMID:Reduced lymphocyte responses to mitogens in natural and experimental trichomoniasis. 222 26

Immunotherapy, with interleukin-2 (IL-2) or IL-2 plus lymphokine-activated killer (LAK) cells, has been used to treat cancer and acquired immunodeficiency syndrome (AIDS) in man. Similarities between feline leukemia virus (FeLV) infection in the cat and human immunodeficiency virus (HIV) infection in man have prompted immunotherapeutic studies in the cat. To develop baseline data on hematological responses to infused IL-2, cats were given daily (1-14 days) i.v. injections of 5 x 10(4) U/kg of recombinant human IL-2 (rHulL-2). Complete blood cell (CBC) counts were done weekly. Red blood cell (RBC), neutrophil, and lymphocyte numbers did not change appreciably over the course of the study. In contrast, rHulL-2 caused an eosinophilia in all but the 1 day treatment group. Treatment for 3 days generated a transient eosinophilia on day 7 that returned to baseline by 3 weeks. Five day and 7 day treatments generated an eosinophilia by day 7 that peaked on day 14 and returned to normal values by day 28. Treatment of cats for 14 days did not increase the magnitude or duration of the eosinophilia beyond the 5 or 7 day treatments. Bone marrow (BM) biopsies from rHulL-2-treated cats revealed a marked selective hyperplasia of eosinophil precursors. In the 5 day treatment group, all maturation stages of eosinophils were elevated by week 1 of treatment. By week 2, the early stages had returned to normal, whereas the late stage cells remained elevated, suggesting an ordered maturation response. Numbers of all eosinophil precursors approximated pretreatment numbers by weeks 3-4. Thus the BM hyperplasia preceded the blood eosinophilia by 1 week, suggesting that an enhanced maturation response of BM eosinophil precursors is a major contributor to the rHulL-2-induced blood eosinophilia. In addition to a maturation signal, rHulL-2 induces a potent activation signal for eosinophils as measured by a decrease in density and an increase in longevity in culture. The significance of the activated eosinophil in the therapeutic or toxicologic response to rHulL-2 infusion is discussed.
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PMID:Human recombinant interleukin-2 induces maturation and activation signals for feline eosinophils in vivo. 223 May 98

Alteration of gene transcription by inhibition of specific transcriptional regulatory proteins is necessary for determining how these factors participate in cellular differentiation. The functions of these proteins can be antagonized by several methods, each with specific limitations. Inhibition of sequence-specific DNA-binding proteins was achieved with double-stranded (ds) phosphorothioate oligonucleotides that contained octamer or kappa B consensus sequences. The phosphorothioate oligonucleotides specifically bound either octamer transcription factor or nuclear factor (NF)-kappa B. The modified oligonucleotides accumulated in cells more effectively than standard ds oligonucleotides and modulated gene expression in a specific manner. Octamer-dependent activation of a reporter plasmid or NF-kappa B-dependent activation of the human immunodeficiency virus (HIV) enhancer was inhibited when the appropriate phosphorothioate oligonucleotide was added to a transiently transfected B cell line. Addition of phosphorothioate oligonucleotides that contained the octamer consensus to Jurkat T leukemia cells inhibited interleukin-2 (IL-2) secretion to a degree similar to that observed with a mutated octamer site in the IL-2 enhancer. The ds phosphorothioate oligonucleotides probably compete for binding of specific transcription factors and may provide anti-viral, immunosuppressive, or other therapeutic effects.
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PMID:Regulation of gene expression with double-stranded phosphorothioate oligonucleotides. 223 44

The transcription of the human immunodeficiency virus type 1 (HIV-1) is under the control of cellular proteins that bind to the viral long terminal repeat (LTR). Among the protein-binding regions of the HIV-1 LTR is the transcription-enhancer region. We show that at least one inducible, C1, and one constitutive, C2, protein can bind to the HIV enhancer in Jurkat cells. The two proteins differ in their surface charge, since they are separable by anion-exchange chromatography. Bivalent cations such as Mg2+ and Zn2+ differentially affect their binding to oligonucleotides which contain the HIV-enhancer domain. Both C1 and C2 proteins also bind to a similar sequence found in the interleukin-2-receptor alpha-subunit enhancer. The inducible C1 protein was partially purified by three chromatographic steps and characterized by u.v. cross-linking as a 47 kDa protein.
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PMID:Characterization of the human immunodeficiency virus type 1 enhancer-binding proteins from the human T-cell line Jurkat. 230 85

We studied the prevalence of four serum factors in individuals at different stages of human immunodeficiency virus-1 (HIV-1) infection. Soluble interleukin-2 receptors (sIL-2R) were elevated in all antibody-positive groups compared with high-risk, antibody-negative controls. Paraproteins, usually of the IgG-kappa isotype, were found in the sera of a significant number of HIV-1-infected individuals as were antibodies to lymphocytes (ALAs). Serum factors that inhibit proliferation of peripheral blood mononuclear cells from healthy donors appear late in the course of infection and were associated with increasing clinical severity. Measurement of these factors may prove to be useful in defining the stages of infection and in predicting the appearance or exacerbation of symptoms. They may also play a role in the development of the HIV-1-induced immune defects that lead to the expression of clinical acquired immunodeficiency syndrome.
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PMID:Serum factors in the progression of human immunodeficiency virus type 1 infection to AIDS. 235 58


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