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)

A rapidly proliferating T-cell line, HCD8, was derived from the peripheral blood lymphocytes of an apparently healthy individual during the course of a T-cell cloning experiment. This T-cell line expressed a very unusual phenotype: CD1+, CD2-, CD3+ (cytoplasmic), CD4-, CD5+, CD7+, CD8-, interleukin-2 receptor (IL-2 R) (p55)-, and T-cell antigen receptor (TCAR) alpha beta-. Assays for reverse transcriptase activity and for human T-lymphotropic retroviral sequences in the cellular DNA were negative, indicating that the cells were not transformed by human T-lymphotropic virus (HTLV)-I, HTLV-II, or human immunodeficiency virus (HIV)-I. Culturing the cells in the differentiation inducing agent 12-O-tetradecanoyl phorbol 13-acetate induced an increased expression of CD3 but no other significant changes in T-cell markers. A small population of CD4-negative and CD8-negative T-lymphocytes exist in human peripheral blood and they exhibit natural killer (NK) and antibody-dependent cell-mediated cytotoxic (ADCC) activity. However, the authors' cell line failed to demonstrate such cytotoxic function. The TCAR gene rearrangement studies showed that both T gamma genes were rearranged while the T beta genes were in the germ line configuration and the T delta genes were deleted. HCD8 strongly expressed the antigens Leu M1 and Ki-1, markers detected only rarely on normal unstimulated human T-cells, but quite consistently found on Reed-Sternberg cells and cells of some large pleomorphic T-cell lymphomas. HCD8 may be used to study the control of Leu M1 and Ki-1 expression in T-cells and it may provide some insight into the cellular origin of the above-mentioned lymphomas.
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PMID:A T-cell line with an unusual phenotype. 255 76

Simian retroviruses closely related to human T-cell leukemia virus (HTLV) were isolated by establishing virus-producing lymphoid cell lines from 7 species of non-human primates. By co-cultivation with human umbilical cord-blood cells and/or in the presence of interleukin-2, lymphoid cell lines were successfully established from the chimpanzee. African green monkey, pig-tailed macaque, red-faced macaque, Formosan monkey, Japanese monkey and bonnet monkey that had antibodies against HTLV antigens. These cell lines reacted with human sera of ATL patients and monoclonal antibodies against p19 and p24 of HTLV antigens. Cellular DNAs contained the provirus sequences homologous to HTLV-I by Southern blot hybridization. Moreover, they produced extracellular type-C virus particles and RNA-dependent DNA polymerase. All of these lymphoid line cells had Tac antigen, interleukin-2 receptor, and those of chimpanzee and red-faced macaque had helper/induced T-cell markers, while those derived from African green monkey had suppressor/cytotoxic T-cell markers. Furthermore, simian HTLV-related viruses of pig-tailed macaque, red-faced macaque and Japanese monkey were transmitted to human lymphocytes on co-cultivation.
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PMID:Isolation of simian retroviruses closely related to human T-cell leukemia virus by establishment of lymphoid cell lines from various non-human primates. 257 38

Currently only limited information is available as to why dominant IgA isotype responses are supported by mucosal T cells in effector tissues. To address this issue directly, gamma delta and alpha beta T cells were isolated from the submandibular gland (SMG) of mice as an example of mucosal effector tissues. Freshly isolated CD3+ T cells from this tissue contained relatively high numbers of activated cells [approximately 10% interleukin-2 receptor (IL-2R)+ cells and 15% of cells in cycle stages S and G2 + M], of which 25% and 75% were gamma delta and alpha beta T cells, respectively. The cytokine-specific quantitative reverse transcriptase-polymerase chain reaction and enzyme-linked immunospot analyses revealed that, although both gamma delta and alpha beta T cells were capable of producing an array of Th1 or Th2 cytokines following stimulation via the T cell receptor-CD3 complex, these mucosal T cells were mainly committed to IL-5 and IL-6 expression in vivo (Th2 type). Both freshly isolated gamma delta and alpha beta T cells expressed mRNA and contained IL-5 and IL-6 spot-forming cells (SFC); however, only the latter exhibited high mRNA levels and SFC for a Th1 cytokine (interferon-gamma). Taken together, the results show that freshly isolated CD3+ T cells from SMG contain activated gamma delta and alpha beta T cells which are programmed to produce IL-5 and IL-6. Thus, SMG, an example of an IgA effector tissue, can be characterized as a Th2-dominant site. However, although both gamma delta and alpha beta T cells express cytokine profiles consistent with a Th2 phenotype, only the latter subset with a CD4+ CD8- phenotype provided effective help for mucosal B cell responses in vitro.
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PMID:Polarized Th2 cytokine expression by both mucosal gamma delta and alpha beta T cells. 758 66

Expression of the interleukin-2 receptor alpha-(IL-2Ralpha-), IL-2Rbeta-, and the recently identified IL-2Rgamma-chain was examined on a wide range of cells of myeloid origin including neutrophils, monocytes, normal bone marrow-derived myeloid progenitors enriched for CD34+ cells, bone marrow blasts obtained from acute myelogenous leukemia (AML) patients, and permanent myeloid leukemia cell lines by reverse transcriptase-polymerase chain reaction and surface membrane analysis using receptor chain-specific monoclonal antibodies and flow cytometry. Expression of the p75 IL-2Rbeta- and the p64 IL-2Rgamma-chain was a common finding in most of the myeloid cell samples investigated, whereas IL-2Ralpha-chain was less frequently expressed. Although the high-affinity IL-2R form (ie, the alpha+, beta+, gamma+ IL-2R form) was detectable in a small minority of primary AML samples as well as the KG-1 cell line and IL-2 binding to these cells was sufficient to initiate signal transduction as evidenced by an increase in overall protein tyrosine phosphorylation and more specifically in tyrosine phosphorylation of the Janus kinase (JAK) 3, in none of these cell types did exposure to IL-2 affect cell growth kinetics. These results suggest that, in myeloid cells, the IL-2R may not stimulate mitogenic responses or that its components may be expressed in a combinational association with receptors for other cytokines and that IL-2Rgamma may play a regulatory role in normal and malignant myelopoiesis possibly independent from IL-2. Because recent studies by others have indicated that the IL-2Rgamma- chain may be shared by the IL-4R, the IL-7R, and most likely the IL-9R, expression of mRNA of these receptor types was also investigated in these cell samples. Surprisingly, in a substantial part of the myeloid lineage cells examined, an IL-2Rgamma+, IL-4R-, IL7R- configuration was noted that was, however, frequently associated with expression of IL-9R. Sharing of IL-9R/IL-2R components was furthermore suggested by inhibition of 125I-IL-2 binding to primary AML cells with excess of unlabeled IL-9.
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PMID:Transcript synthesis and surface expression of the interleukin-2 receptor (alpha-, beta-, and gamma-chain) by normal and malignant myeloid cells. 863 Apr 6

The state of activation of the immune system may be an important factor which renders a host more receptive to human immunodeficiency virus (HIV) and more vulnerable to its effects. To explore this issue with a practical in vivo model, we developed a modified protocol of HIV infection in hu-PBL-SCID mice. First, we assessed the time course of activation of human peripheral blood lymphocytes (hu-PBL) in the peritoneal cavity of SCID mice. At 2 to 24 h after the intraperitoneal injection into SCID mice, there was a clear-cut increase in the percentage of hu-PBL expressing early activation markers (CD69), concomitant with the release of soluble intercellular adhesion molecule-1 (sICAM-1) and the soluble interleukin-2 receptor (sIL-2R) and with the accumulation of mRNAs for a number of human cytokines. At 2 weeks, virtually all of the hu-PBL expressed the memory phenotype (CD45RO) and HLA-DR antigens as well. Cells collected from the SCID mouse peritoneum at 2 and 24 h after transplantation were fully susceptible to in vitro infection with HIV type 1 (HIV-1) in the absence of either IL-2 or mitogens. The injection of HIV into hu-PBL-SCID mice at 2 h after reconstitution resulted in a generalized and productive HIV infection of the xenochimeras. This early HIV-1 infection resulted in a dramatic depletion of human CD4+ cells and in decreased levels of sICAM-1 (in the peritoneal lavage fluid) as well as of sIL-2R and immunoglobulins M and A (in the serum). Enzyme-linked immunosorbent assay and/or reverse transcriptase PCR analysis showed higher levels of IL-4, IL-5, and IL-10 in the HIV-infected animals than in control hu-PBL-SCID mice, while gamma interferon levels in the two groups were comparable. When we compared the current model of HIV-1 infection at 2 weeks after the intraperitoneal injection of the hu-PBL in the SCID mice with the model described here, we found that the majority of immune dysfunctions induced in the 2-h infection of the xenochimeras are not inducible in the 2-week infection. This supports the concept that the state of activation of human cells at the moment of the in vivo infection with HIV-1 is a crucial factor in determining the immune derangement observed in AIDS patients. These results show that some immunological dysfunctions induced by HIV infection in AIDS patients can be mimicked in this xenochimeric model. Thus, the hu-PBL-SCID mouse model may be useful in exploring, in vivo, the relevance of hu-PBL activation and differentiation in HIV-1 infection and for testing therapeutic intervention directed towards either the virus or the immune system.
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PMID:T-cell dysfunctions in hu-PBL-SCID mice infected with human immunodeficiency virus (HIV) shortly after reconstitution: in vivo effects of HIV on highly activated human immune cells. 889 19

Recent studies have suggested that the membrane proximal region of the cytoplasmic domain of the erythropoietin receptor and other members of the cytokine receptor superfamily may be required for signal transduction. Expression of several deletion mutants of the erythropoietin receptor in Ba/F3 cells showed that a region with homology to the interleukin-2 receptor beta-chain which includes Box 2 is not essential for erythropoietin-dependent cell proliferation. However, a region between Box 1 and Box 2 contains essential residues for proliferative response. Expression of mutant receptors was confirmed by reverse transcriptase-PCR analysis and by Western blotting, which also showed no evidence for expression of endogenous wild-type receptor. These findings are in direct conflict with previously reported mutagenesis studies of the erythropoietin receptor suggesting that mitogenesis may be channelled through more than one pathway depending on the complement of signaling molecules expressed in the cell.
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PMID:Conserved region of the cytoplasmic domain is not essential for erythropoietin-dependent growth. 893 18

Although the immunosuppressive agents used clinically modulate acute rejection of organ allografts, their ability to prevent chronic rejection has been less clear. To ascertain the effects of prolonged maintenance treatment with cyclosporine (CsA) and mycophenolate mofetil, we examined sequential patterns of cytokine regulation by reverse transcriptase polymerase chain reaction in long-surviving renal allografts in treated recipients. In renal allografts in animals on long-term CsA therapy, there is important up-regulation of transforming growth factor-beta, Hsp70, and endothelin as compared with control animals. Conversely, interleukin-2 receptor, interferon-gamma, and tumor necrosis factor-alpha in kidney grafts in this group were expressed at lower levels compared with those noted in chronically rejecting grafts in control animals that had received only CsA for 10 days after transplantation. Morphologically, the long-term CsA-treated kidneys had more extensive arterial obliterative changes and glomerulosclerosis after 24 weeks than control organs; these changes can presumably be attributed to the nephrotoxic effects of this drug combined with the progressive changes of chronic rejection. In contrast, mycophenolate mofetil inhibited the production of all lymphocyte and macrophage-derived cytokines throughout the entire follow-up period. Allograft kidneys in these latter recipients showed no late morphological abnormalities. This agent may be important clinically in preventing chronic rejection.
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PMID:Sequential cytokine expression in renal allografts in rats immunosuppressed with maintenance cyclosporine or mycophenolate mofetil. 893 88

The gamma common (gamma c) chain is a partner in several interleukin receptor complexes, including the interleukin-2 receptor (IL-2R), IL-4R, and IL-7R. Mutations in the gamma c gene are associated with X-linked severe combined immunodeficiency (SCID). Using reverse transcriptase-PCR, we examined the level of mRNA-encoding gamma c and its partners in mouse pluripotent hematopoietic stem cells (PHSCs), which repopulate both bone marrow and thymus. We also assayed developing lymphocytes to define which, if any, IL-R complexes are expressed at the earliest stage of T and B lymphocyte maturation. RNA extracted from bone marrow-derived PHSCs did not contain detectable levels of mRNA-encoding IL-7R alpha. However, the most primitive (CD4- CD8-) T cells from the thymus and the most primitive (c-kit+ B220+) B cells from bone marrow contained high levels of IL-7R alpha mRNA. There were no detectable differences between PHSCs and primitive or more mature T and B cells for expression of gamma c mRNA. We conclude that the onset of IL-7R formation occurs at the earliest stage of differentiation of T and B lymphocytes. Our findings are consistent with the hypothesis that the absence of an intact IL-7R (IL-7R alpha and gamma c) may be a critical loss that interrupts lymphopoiesis.
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PMID:Interleukin-7R alpha mRNA expression increases as stem cells differentiate into T and B lymphocyte progenitors. 909 Dec 97

To investigate the role of human gingival fibroblasts (HGF), the major constituents of gingival tissue in periodontal inflammatory disease, the expression of interleukin-2 receptor (IL-2R) alpha, beta, and gamma chains was examined. Immunohistochemistry showed a pronounced accumulation of CD8(+) T cells in the inflamed lamina propria of gingival tissue from patients with adult periodontitis. HGF express IL-2Rbeta and IL-2Rgamma at mRNA and protein levels, but the expression of IL-2Ralpha could not be detected, as assessed by reverse transcriptase-polymerase chain reaction and flow cytometry. IL-2Rbeta, and -gamma expressed on HGF were functionally active, as addition of neutralizing anti-IL-2Rbeta and -gamma antibodies caused inhibition of the IL-2-induced production of monocyte chemoattractant protein-1 (MCP-1), and addition of IL-2 induced phosphorylation of Janus tyrosine kinase 3, which is critical in signaling through IL-2Rgamma in HGF. The IL-2-induced MCP-1 production was significantly inhibited by pretreatment with neutralizing antibody to IL-15. Addition of IL-2 also induced a marked up-regulation of the expression of intercellular adhesion molecule-1 (ICAM-1) on the surface of HGF, which in turn, significantly augmented the adhesion of human neutrophils, which were inhibited by an anti-ICAM-1 antibody. These results suggest that HGF express functional IL-2Rbetagamma, respond to IL-2 from infiltrated T cells, and actively participate in the inflammatory process in the periodontal region and that IL-15 produced by HGF sustains IL-2-mediated signaling in HGF.
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PMID:Expression of IL-2 receptor beta and gamma chains by human gingival fibroblasts and up-regulation of adhesion to neutrophils in response to IL-2. 1294 38

Beta-propeller protein-associated neurodegeneration (BPAN), also known as static encephalopathy of childhood with neurodegeneration in adulthood (SENDA), is a subtype of neurodegeneration with brain iron accumulation (NBIA). BPAN is caused by mutations in an X-linked gene WDR45 that is involved in autophagy. BPAN is characterized by developmental delay or intellectual disability until adolescence or early adulthood, followed by severe dystonia, parkinsonism, and progressive dementia. Brain magnetic resonance imaging (MRI) shows iron deposition in the bilateral globus pallidus (GP) and substantia nigra (SN). Clinical manifestations and laboratory findings in early childhood are limited. We report a 3-year-old girl with BPAN who presented with severe developmental delay and characteristic facial features. In addition to chronic elevation of serum aspartate transaminase, lactate dehydrogenase, creatine kinase, and soluble interleukin-2 receptor, she had persistent elevation of neuron specific enolase (NSE) in serum and cerebrospinal fluid. MRI using susceptibility-weighted imaging (SWI) demonstrated iron accumulation in the GP and SN bilaterally. Targeted next-generation sequencing identified a de novo splice-site mutation, c.831-1G>C in WDR45, which resulted in aberrant splicing evidenced by reverse transcriptase-PCR. Persistent elevation of NSE and iron deposition on SWI may provide clues for diagnosis of BPAN in early childhood.
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PMID:Elevation of neuron specific enolase and brain iron deposition on susceptibility-weighted imaging as diagnostic clues for beta-propeller protein-associated neurodegeneration in early childhood: Additional case report and review of the literature. 2648 52


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