Linked Life Data

10878338

Source:http://linkedlifedata.com/resource/pubmed/id/10878338

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-8-3
pubmed:abstractText
In neoplastic cells of EBV-positive lymphoid malignancies latent membrane protein (LMP1) is expressed. Because no adequate cellular immune response can be detected against LMP1, we investigated whether LMP1 had a direct effect on T lymphocyte activation. In this study we show that nanogram amounts of purified recombinant LMP1 (rLMP1) strongly suppresses activation of T cells. By sequence alignment two sequences (LALLFWL and LLLLAL) in the first transmembrane domain of LMP1 were identified showing strong homology to the immunosuppressive domain (LDLLFL) of the retrovirus-encoded transmembrane protein p15E. The effects of rLMP1 and LMP1-derived peptides were tested in T cell proliferation and NK cytotoxicity assays and an Ag-induced IFN-gamma release enzyme-linked immunospot assay. LMP1 derived LALLFWL peptides showed strong inhibition of T cell proliferation and NK cytotoxicity, while acetylated LALLFWL peptides had an even stronger effect. In addition, Ag-specific IFN-gamma release was severely inhibited. To exert immunosuppressive effects in vivo, LMP1 has to be excreted from the cells. Indeed, LMP1 was detected in supernatant of EBV-positive B cell lines (LCL), and differential centrifugation in combination with Western blot analysis of the pellets indicated that LMP1 is probably secreted by LCL in the form of exosomes. The amount of secreted LMP1 in B cell cultures is well below the immunosuppressive level observed with rLMP1. Our results demonstrate direct immunosuppressive properties of LMP1 (fragments) and suggest that EBV-positive tumor cells may actively secrete LMP1 and thus mediate immunosuppressive effects on tumor-infiltrating lymphocytes. Moreover, we demonstrate, for the first time, that transmembrane protein-mediated immunosuppression is not solely restricted to RNA tumor viruses, but can also be found in DNA tumor viruses.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
165
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
663-70
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed-meshheading:10878338-Amino Acid Sequence, pubmed-meshheading:10878338-Cell Fractionation, pubmed-meshheading:10878338-Cell Line, Transformed, pubmed-meshheading:10878338-Cell-Free System, pubmed-meshheading:10878338-Cytotoxicity, Immunologic, pubmed-meshheading:10878338-Epitopes, T-Lymphocyte, pubmed-meshheading:10878338-Herpesvirus 4, Human, pubmed-meshheading:10878338-Humans, pubmed-meshheading:10878338-Immunosuppressive Agents, pubmed-meshheading:10878338-Killer Cells, Natural, pubmed-meshheading:10878338-Lymphocyte Activation, pubmed-meshheading:10878338-Molecular Sequence Data, pubmed-meshheading:10878338-Peptide Fragments, pubmed-meshheading:10878338-Protein Structure, Tertiary, pubmed-meshheading:10878338-Recombinant Proteins, pubmed-meshheading:10878338-T-Lymphocytes, pubmed-meshheading:10878338-Tetanus Toxoid, pubmed-meshheading:10878338-Tumor Cells, Cultured, pubmed-meshheading:10878338-Viral Matrix Proteins
pubmed:year
2000
pubmed:articleTitle
Direct immunosuppressive effects of EBV-encoded latent membrane protein 1.
pubmed:affiliation
Department of Pathology, Academic Hospital, Vrije Universiteit, Amsterdam, The Netherlands. d.dukers@azvu.nl
pubmed:publicationType
Journal Article