Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin 12 (IL-12) activates natural killer (NK) and T cells with the secondary synthesis and release of interferon-gamma (IFN-gamma) and other cytokines. IL-12-induced organ alterations are reported for mice and the pathogenetic role of IFN-gamma is investigated by the use of mice deficient in the IFN-gamma receptor (IFN-gamma R-/-). IL-12 caused a rapid infiltration of liver and splenic red pulp with activated macrophages; this and increased NK cells resulted in a fivefold increase of splenic weight in wild-type mice. Splenomegaly was associated with myelosuppression and decreasing peripheral leukocyte counts. IL-12-induced changes in wild-type mice were associated with markedly increased IFN-gamma serum levels and up-regulation of major histocompatibility complex (MHC) class I and II expression in various epithelia. IL-12 induced a qualitatively similar macrophage infiltration in IFN-gamma R-/- mice, less marked splenomegaly (to 2 x normal), and no MHC upregulation. Strikingly increased vascular endothelial intercellular adhesion molecule-1 expression was apparent in both IFN-gamma R-/- and IFN-gamma R+/+ mice. Restricted to mutant mice was a severe, invariably lethal, interstitial, and perivascular pulmonary macrophage infiltration with diffuse pulmonary edema. Extensive quantitative reverse transcriptase polymerase chain reaction analysis revealed an increase of only IL-6 and IL-10 pulmonary gene transcripts in IFN-gamma R-/- mice compared with wild-type mice. IL-12-induced myelosuppression is due to IFN-gamma-release from NK cells and T cells, and is associated with macrophage activation and distinct MHC class I and II antigen upregulation. The pulmonary pathology in IFN-gamma R-/- mice, however, reveals a toxic potential for IL-12 and suggests that endogenous IFN-gamma plays a protective role in preventing fatal pulmonary disease in these mice.
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PMID:Role of interferon-gamma in interleukin 12-induced pathology in mice. 749 76

We have studied the effect of poly(ADP-ribose) synthetase on the interferon-gamma (IFN-gamma)-inducible expression of major histocompatibility complex (MHC) class II molecules. We constructed an expression plasmid capable of expressing either a sense RNA (MT-ARS) or an antisense RNA (pAS-FL or pAS-5') for poly(ADP-ribose) synthetase. We transfected the plasmid into mouse or human macrophage tumor cells and examined the effect on the expression of MHC class II molecules. The IFN-gamma-inducible expression of MHC class II gene was considerably reduced in transformant clones (A-2, B-2), in which the synthetase was highly expressed, whereas the depletion of the synthetase due to the expression of antisense RNA for the synthetase amplified the expression of MHC class II molecules. The results indicate that the level of the synthetase critically regulates the IFN-gamma-inducible MHC class II molecules. Next, we analyzed DNase I hypersensitive sites (DHS) of mouse MHC class II, I-A beta gene and found two sites, one in the promoter region and the other one in the first intron. The DHS in first intron was less sensitive towards DNase I attack in transformant clones (A-2, B-2) in which the synthetase was synthesized in a large quantity. Thus we constructed two beta-galactosidase reporter genes, one (A beta 2.0kb-lac z) containing the promoter region to a part of the second exon of the class II gene, and the other (A beta pro-lac z) containing the promoter region of the class II gene alone. The expression of the reporter gene was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) and found that the expression of A beta 2.0kb-lac z was suppressed in the transformant clones (A-2, B-2) relevant to control cells but the expression of A beta pro-lac z was the same level among those cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of poly(ADP-ribose) synthetase on the expression of major histocompatibility complex (MHC) class II genes. 757 32

HLA-G limited polymorphic gene maps to the human major histocompatibility complex (MHC) class I subregion and encodes the molecule which is the only MHC class I antigen expressed on cytotrophoblast cells at the maternal-fetal interface. In this tissue, HLA-G primary mRNA is differentially spliced. We have used a sensitive hot start reverse transcriptase-polymerase chain reaction (RT-PCR) technique to investigate the expression of HLA-G gene in first trimester trophoblasts and adult peripheral blood cells. PCR amplification with HLA-G primers specific of exon 3 has enabled us to demonstrate a novel alternatively spliced form of HLA-G mRNA present in fetal first trimester trophoblasts and lacking exon 4 (HLA-G4). Cloning the whole PCR product and hybridizing recombinant bacterial colonies with specific probes has permitted evaluation of HLA-G4 vs. full length mRNA frequency at approximately 1:200. Moreover, the presence of HLA-G transcripts was found at a very weak level in adult peripheral blood lymphocytes and equally in B- and T-cell populations. These results are relevant in the context of immune tolerance and in the potential use of HLA-G transcripts as a marker for RT-PCR detection of the fetal cells in maternal as a marker for RT-PCR detection of the fetal cells in maternal blood.
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PMID:HLA-G mRNA forms in human trophoblasts and peripheral blood lymphocytes: potential use in prenatal diagnosis. 758 1

Neurons have evolved strategies to evade immune surveillance that include an inability to synthesize the heavy chain of the class I major histocompatibility complex (MHC), proteins that are necessary for cytotoxic T lymphocyte (CTL) recognition of target cells. Multiple viruses have taken advantage of the lack of CTL-mediated recognition and killing of neurons by establishing persistent neuronal infections and thereby escaping attack by antiviral CTL. We have expressed a class I MHC molecule (Db) in neurons of transgenic mice using the neuron-specific enolase (NSE) promoter to determine the pathogenic consequences of CTL recognition of virally infected, MHC-expressing central nervous system (CNS) neurons. The NSE-Db transgene was expressed in H-2b founder mice, and transgene-derived messenger RNA was detected by reverse transcriptase-polymerase chain reaction in transgenic brains from several lines. Purified primary neurons from transgenic but not from nontransgenic mice adhered to coverslips coated with a conformation-dependent monoclonal antibody directed against the Dv molecule and presented viral peptide to CTL in an MHC-restricted manner, indicating that the Db molecule was expressed on transgenic neurons in a functional form. Transgenic mice infected with the neurotropic lymphocytic choriomeningitis virus (LCMV) and given anti-LCMV, MHC-restricted CTL displayed a high morbidity and mortality when compared with controls receiving MHC-mismatched CTL or expressing alternative transgenes. After CTL transfer, transgenic brains showed an increased number of CD8+ cells compared with nontransgenic controls as well as an increased rate of clearance of infectious virus from the CNS. Additionally, an increase in blood-brain barrier permeability was detected during viral clearance in NSE-Db transgenic mice and lasted several months after clearance of virus from neurons. In contrast, LCMV-infected, nontransgenic littermates and mice expressing other gene products from the NSE promoter showed no CNS disease, no increased intraparenchymal CTL, and no blood-brain barrier damage after the adoptive transfer of antiviral CTL. Our study indicates that viral infections and CTL-CNS interactions may induce blood-brain barrier disruptions and neurologic disease by a "hit-and-run" mechanism, triggering a cascade of pathogenic events that proceeds in the absence of continual viral stimulation.
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PMID:Consequences of cytotoxic T lymphocyte interaction with major histocompatibility complex class I-expressing neurons in vivo. 759 91

In the present study, the expression of the CD4 molecule on murine egg plasma membrane was confirmed by the indirect immunofluorescence (IIF) method. The full-length CD4 cDNA from murine eggs was synthesised by the reverse transcriptase-polymerase chain reaction (RT-PCR) method and its authenticity verified by Southern blot hybridisation using an end-labelled internal oligonucleotide. The results of DNA sequencing showed that the nucleotide sequence of the cDNA of CD4 from murine egg mRNA was identical to that of immune T cells. To demonstrate the direct interaction of CD4 from murine egg with murine sperm cells bearing MHC (major histocompatibility complex) class II molecule, we employed a baculovirus expression system to generate CD4 on the surface of Spodoptera frugiperda (Sf9) cells. Expression of CD4 on Sf9 cells infected with Autographa californica nuclear polyhedrosis virus (AcNPV)-CD4 was demonstrated by IIF and immunoblotting. The CD4-expressing Sf9 cells adhered to MHC class II-bearing sperm cells since the adhesion was specifically blocked by anti-CD4 monoclonal antibody (mAb) or anti-monomorphic region of MHC class II mAb. Taking our previous and present experimental results together, they strongly suggest that intercellular membrane adhesion between two gametes at the fusion step in fertilisation is mediated by the MHC class II molecule located on the posterior region of the sperm head and the CD4 molecule on egg plasma membrane.
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PMID:Molecular structure and function of CD4 on murine egg plasma membrane. 761 76

Whether neurons express major histocompatibility complex (MHC) class I genes has not been firmly established. The techniques of confocal laser microscopy, patch clamp electrophysiology, and reverse transcriptase-polymerase chain reaction were combined here to directly examine the inducibility of MHC class I genes in individual cultured rat hippocampal neurons. Transcription of MHC class I genes was very rare in neurons with spontaneous action potentials. In electrically silent neurons, transcription was noted, with expression of beta 2-microglobulin under tighter control than in class I heavy chain molecules. Surface expression of class I molecules occurred only in electrically silent neurons treated with interferon gamma. Immunosurveillance by cytotoxic T cells may be focused on functionally impaired neurons.
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PMID:Induction of MHC class I genes in neurons. 748 56

Intestinal epithelial cells of the neonatal rat and mouse have been shown to express a major histocompatibility complex (MHC) class I-like Fc receptor, or FcRn, which transports IgG in an apical to basolateral direction. Previous studies have suggested the possible expression of this receptor beyond the neonatal period within the liver. Since bile contains high levels of IgG, we sought to determine whether the FcRn was functionally expressed by adult rat hepatocytes. Using primers specific for FcRn, which did not cross hybridize with MHC class I transcripts, FcRn DNA was amplified by reverse transcriptase polymerase chain reaction from RNA of adult rat hepatocytes. This RNA contained functional FcRn transcripts as it encoded a beta 2-microglobulin-associated cell surface protein as determined by immunoprecipitation of biotinylated cell surface proteins with a polyclonal anti-FcRn specific antiserum. Western blotting of hepatocyte canalicular (apical) and sinusoidal (basolateral) plasma membranes with an FcRn-specific monoclonal antibody further confirmed the protein expression and suggested that FcRn was enriched on the canalicular surface membranes. FcRn, on the surface of hepatocytes, was biologically functional as it bound Fc fragments of IgG at pH 6.0 but not 8.0, which is the same pH dependence observed for FcRn in rat neonatal enterocytes. Thus, FcRn is functionally expressed outside of the neonatal period on the canalicular cell surface of adult hepatocytes. This suggests that hepatocyte FcRn may bind luminal IgG, providing a potential functional communication between parenchymal immune cells and bile.
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PMID:A major histocompatibility complex class I-related Fc receptor for IgG on rat hepatocytes. 773 3

As shown recently, CD3+/TcR+ functional T lymphocytes can be derived in culture from embryonic liver cell precursors at a gestational age (6-8 weeks) preceding the colonization of the epithelial thymus. In this report, we analyzed the V beta repertoire of T lymphocytes derived from embryonic liver by applying a quantitative reverse transcriptase-polymerase chain reaction technique. To this end, oligonucleotide primers for C alpha or the various human V beta have been used to study both freshly derived embryonic liver cell suspensions and CD3+/TcR+ populations derived after approximately 6 weeks upon stimulation with 1% phytohemagglutinin and culture in 100 units/ml recombinant interleukin-2. In order to exclude possible contaminations with mother-derived T lymphocytes, only T cells displaying both X and Y chromosomal sequences (i.e. derived from male embryos) were further analyzed. While neither C alpha nor the various V beta could be detected in fresh liver cells, C alpha and the large majority of V beta were detected in in vitro cultured populations. The levels of the various V beta expressed by embryo-derived T cells was similar to that detected in adult peripheral blood-derived T lymphocytes. These experiments indicate that the immature liver precursors can potentially give rise in vitro to T cells which express a wide V beta repertoire and may provide a suitable in vitro system for the analysis of the selection processes mediated by either major histocompatibility complex antigen or superantigens.
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PMID:Expression of a wide T cell receptor V beta repertoire in human T lymphocytes derived in vitro from embryonic liver cell precursors. 808 40

The HLA-G monomorphic, nonclassical class I gene encodes the major histocompatibility complex (MHC) molecule, which is the only MHC antigen expressed on cytotrophoblast cells of placenta. In this work, we have investigated expression of the HLA-G gene in fetal tissues and adult peripheral blood cells by using a sensitive hot-start reverse transcriptase PCR technique. PCR amplification with HLA-G primers specific for exon 3 has enabled us to demonstrate an alternatively spliced form of HLA-G mRNA present in fetal first trimester trophoblasts and lacking exon 4 (HLA-G.3-5). This low abundance transcript (approximately 1:200) in comparison to full-length mRNA may encode the protein that excludes the alpha 3 domain and by conformational changes may present a different ability to bind to peptides. Moreover, expression of the HLA-G transcript was found in adult peripheral lymphocytes and equally in B- and T-cell populations. These results are discussed in the context of the fetal-maternal relationship presented by HLA-G gene products.
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PMID:An alternatively spliced form of HLA-G mRNA in human trophoblasts and evidence for the presence of HLA-G transcript in adult lymphocytes. 818 92

Multilineage donor-derived hematopoietic cell chimerism is a persistent feature of spontaneously tolerant mouse liver allograft recipients. We have shown previously that normal liver-derived precursors of "chimeric" dendritic cells (DC) propagated in vitro migrate in vivo to T-dependent areas of allogeneic lymphoid tissue, where they or their progeny appear to persist indefinitely. In this study, granulocyte-macrophage colony-stimulating factor (GM-CSF)+interleukin-4 (IL-4) were used to propagate DC progenitors from freshly isolated mouse bone marrow. The progenitor cells gave rise in 7-10 days to potent antigen-presenting cells (APC) that stimulated naive allogeneic T cells in primary mixed leukocyte cultures (MLC). The culture method, together with the reverse transcriptase-polymerase chain reaction (RT-PCR) for the detection of donor and recipient strain major histocompatibility complex (MHC) class II mRNA was used to test whether donor-derived DC could be propagated from the bone marrow of unmodified, orthotopic liver allograft recipients. Freshly isolated bone marrow from these transplanted animals contained small numbers of donor cells and responded to GM-CSF+IL-4 stimulation. In addition to cells expressing recipient (B10) phenotype (H-2Kb+; Iab+), a minor population of donor (B10.BR)-derived cells (H-2Kk+; Iak) were also propagated from liver graft recipients euthanized two weeks posttransplant. DC sorted from these cultures exhibited stimulatory activity for recipient strain T cells consistent with a low level (< 1%) of donor DC propagation. The immunologic role of donor-derived DC progenitors in liver allograft recipients and its relation to the induction and maintenance of donor-specific unresponsiveness remains to be determined.
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PMID:Identification of donor-derived dendritic cell progenitors in bone marrow of spontaneously tolerant liver allograft recipients. 854 89


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