Base de dados : MEDLINE
Pesquisa : D12.776.395.550.448.180 [Categoria DeCS]
Referências encontradas : 258 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 26 ir para página                         

  1 / 258 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28386908
[Au] Autor:Meazza R; Falco M; Marcenaro S; Loiacono F; Canevali P; Bellora F; Tuberosa C; Locatelli F; Micalizzi C; Moretta A; Mingari MC; Moretta L; Aricò M; Bottino C; Pende D
[Ad] Endereço:Dipartimento delle Terapie Oncologiche Integrate, IRCCS AOU San Martino-IST, Genoa, Italy.
[Ti] Título:Inhibitory 2B4 contributes to NK cell education and immunological derangements in XLP1 patients.
[So] Source:Eur J Immunol;47(6):1051-1061, 2017 Jun.
[Is] ISSN:1521-4141
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:X-linked lymphoproliferative disease 1 (XLP1) is an inherited immunodeficiency, caused by mutations in SH2D1A encoding Signaling Lymphocyte Activation Molecule (SLAM)-associated protein (SAP). In XLP1, 2B4, upon engagement with CD48, has inhibitory instead of activating function. This causes a selective inability of cytotoxic effectors to kill EBV-infected cells, with dramatic clinical sequelae. Here, we investigated the NK cell education in XLP1, upon characterization of killer Ig-like receptor (KIR)/KIR-L genotype and phenotypic repertoire of self-HLA class I specific inhibitory NK receptors (self-iNKRs). We also analyzed NK-cell cytotoxicity against CD48 or CD48 KIR-ligand matched or autologous hematopoietic cells in XLP1 patients and healthy controls. XLP1 NK cells may show a defective phenotypic repertoire with substantial proportion of cells lacking self-iNKR. These NK cells are cytotoxic and the inhibitory 2B4/CD48 pathway plays a major role to prevent killing of CD48 EBV-transformed B cells and M1 macrophages. Importantly, self-iNKR defective NK cells kill CD48 targets, such as mature DCs. Self-iNKR NK cells in XLP1 patients are functional even in resting conditions, suggesting a role of the inhibitory 2B4/CD48 pathway in the education process during NK-cell maturation. Killing of autologous mature DC by self-iNKR defective XLP1 NK cells may impair adaptive responses, further exacerbating the patients' immune defect.
[Mh] Termos MeSH primário: Células Matadoras Naturais/imunologia
Transtornos Linfoproliferativos/imunologia
Transtornos Linfoproliferativos/fisiopatologia
Receptores de Células Matadoras Naturais/imunologia
Família de Moléculas de Sinalização da Ativação Linfocitária/metabolismo
[Mh] Termos MeSH secundário: Antígeno CD48/imunologia
Antígeno CD48/metabolismo
Genes MHC Classe I
Seres Humanos
Células Matadoras Naturais/metabolismo
Ativação Linfocitária
Canais de Potássio Corretores do Fluxo de Internalização/imunologia
Receptores Imunológicos/metabolismo
Transdução de Sinais
Proteína Associada à Molécula de Sinalização da Ativação Linfocitária/metabolismo
Família de Moléculas de Sinalização da Ativação Linfocitária/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CD244 protein, human); 0 (CD48 Antigen); 0 (CD48 protein, human); 0 (Kcnj10 (channel)); 0 (Potassium Channels, Inwardly Rectifying); 0 (Receptors, Immunologic); 0 (Receptors, Natural Killer Cell); 0 (Signaling Lymphocytic Activation Molecule Associated Protein); 0 (Signaling Lymphocytic Activation Molecule Family)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170408
[St] Status:MEDLINE
[do] DOI:10.1002/eji.201646885


  2 / 258 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28337051
[Au] Autor:Jia B; Zhao C; Li G; Kong Y; Ma Y; Wang Q; Wang B; Zeng H
[Ad] Endereço:Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100015, China.
[Ti] Título:A Novel CD48-Based Analysis of Sepsis-Induced Mouse Myeloid-Derived Suppressor Cell Compartments.
[So] Source:Mediators Inflamm;2017:7521701, 2017.
[Is] ISSN:1466-1861
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Myeloid-derived suppressor cells (MDSCs) are a heterogeneous subset of cells that expands dramatically in many disease states and can suppress T-cell responses. MDSCs mainly include monocytic and granulocytic subpopulations that can be distinguished in mice by the expression of Ly6G and Ly6C cell surface markers. This identification system has been validated in experimental tumor models, but not in models of inflammation-associated conditions such as sepsis. We challenged growth factor independent 1 transcription repressor green fluorescent protein (Gfi1:GFP) knock-in reporter mice with cecal ligation and puncture surgery and found that CD11b Ly6G Ly6C MDSCs in this sepsis model comprised both monocytic and granulocytic MDSCs. The evidence that conventional Ly6G/Ly6C marker analysis may not be suited to study of inflammation-induced MDSCs led to the development of a novel strategy of distinguishing granulocytic MDSCs from monocytic MDSCs in septic mice by expression of CD48. Application of this novel model should help achieve a more accurate understanding of the inflammation-induced MDSC activity.
[Mh] Termos MeSH primário: Antígeno CD48/metabolismo
Células Supressoras Mieloides/citologia
Sepse/metabolismo
[Mh] Termos MeSH secundário: Animais
Antígeno CD48/genética
Membrana Celular/metabolismo
Proteínas de Ligação a DNA/metabolismo
Modelos Animais de Doenças
Genes Reporter
Granulócitos/citologia
Granulócitos/metabolismo
Proteínas de Fluorescência Verde/metabolismo
Inflamação
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Monócitos/metabolismo
Células Mieloides/metabolismo
Sepse/fisiopatologia
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CD48 Antigen); 0 (Cd48 protein, mouse); 0 (DNA-Binding Proteins); 0 (Gfi1 protein, mouse); 0 (Transcription Factors); 147336-22-9 (Green Fluorescent Proteins)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170325
[St] Status:MEDLINE
[do] DOI:10.1155/2017/7521701


  3 / 258 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:27581174
[Au] Autor:McArdel SL; Brown DR; Sobel RA; Sharpe AH
[Ad] Endereço:Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115.
[Ti] Título:Anti-CD48 Monoclonal Antibody Attenuates Experimental Autoimmune Encephalomyelitis by Limiting the Number of Pathogenic CD4+ T Cells.
[So] Source:J Immunol;197(8):3038-3048, 2016 Oct 15.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:CD48 (SLAMF2) is an adhesion and costimulatory molecule constitutively expressed on hematopoietic cells. Polymorphisms in CD48 have been linked to susceptibility to multiple sclerosis (MS), and altered expression of the structurally related protein CD58 (LFA-3) is associated with disease remission in MS. We examined CD48 expression and function in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. We found that a subpopulation of CD4 T cells highly upregulated CD48 expression during EAE and were enriched for pathogenic CD4 T cells. These CD48 CD4 T cells were predominantly CD44 and Ki67 , included producers of IL-17A, GM-CSF, and IFN-γ, and were most of the CD4 T cells in the CNS. Administration of anti-CD48 mAb during EAE attenuated clinical disease, limited accumulation of lymphocytes in the CNS, and reduced the number of pathogenic cytokine-secreting CD4 T cells in the spleen at early time points. These therapeutic effects required CD48 expression on CD4 T cells but not on APCs. Additionally, the effects of anti-CD48 were partially dependent on FcγRs, as anti-CD48 did not ameliorate EAE or reduce the number of cytokine-producing effector CD4 T cells in Fcεr1γ mice or in wild-type mice receiving anti-CD16/CD32 mAb. Our data suggest that anti-CD48 mAb exerts its therapeutic effects by both limiting CD4 T cell proliferation and preferentially eliminating pathogenic CD48 CD4 T cells during EAE. Our findings indicate that high CD48 expression is a feature of pathogenic CD4 T cells during EAE and point to CD48 as a potential target for immunotherapy.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/uso terapêutico
Linfócitos T CD4-Positivos/efeitos dos fármacos
Antígeno CD48/imunologia
Encefalomielite Autoimune Experimental/terapia
Células-Tronco Hematopoéticas/fisiologia
Imunoterapia/métodos
Esclerose Múltipla/terapia
[Mh] Termos MeSH secundário: Animais
Linfócitos T CD4-Positivos/imunologia
Antígeno CD48/genética
Proliferação Celular
Células Cultivadas
Encefalomielite Autoimune Experimental/genética
Encefalomielite Autoimune Experimental/imunologia
Predisposição Genética para Doença
Seres Humanos
Contagem de Linfócitos
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Esclerose Múltipla/genética
Esclerose Múltipla/imunologia
Polimorfismo Genético
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (CD48 Antigen)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171015
[Lr] Data última revisão:
171015
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:160902
[St] Status:MEDLINE


  4 / 258 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26926492
[Au] Autor:Wuttge DM; Andreasson A; Tufvesson E; Johansson ÅC; Scheja A; Hellmark T; Hesselstrand R; Truedsson L
[Ad] Endereço:a Section of Rheumatology, Department of Clinical Sciences, Lund University and Skåne University Hospital , Lund , Sweden.
[Ti] Título:CD81 and CD48 show different expression on blood eosinophils in systemic sclerosis: new markers for disease and pulmonary inflammation?
[So] Source:Scand J Rheumatol;45(2):107-13, 2016.
[Is] ISSN:1502-7732
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: In systemic sclerosis (SSc)-related interstitial lung disease (ILD), elevated eosinophil counts in bronchoalveolar lavage are associated with a worse outcome. We hypothesized that eosinophils may be activated in the peripheral circulation, thereby increasing their recruitment to affected tissues and contributing to inflammation and fibrosis. The aim of this study was to characterize the blood eosinophils in SSc patients. METHOD: Expression levels of surface markers CD11b, CD44, CD48, CD54, CD69, CD81, and HLA-DR on CD16(low)CD9(high)-expressing eosinophils were measured by flow cytometry in whole blood from SSc patients (n = 32) and controls (n = 11). RESULTS: Expression levels of CD54, CD69, and HLA-DR were undetectable in all groups. CD44 and CD11b expression levels were similar between groups. CD81 expression was lower in patients compared to controls independent of disease duration (p = 0.001). CD48 expression was increased in patients with a short disease duration (< 2 years) compared to both controls (p = 0.042) and patients with longer disease duration (≥ 2 years; p = 0.027). In patients with short disease duration, increased CD48 expression was associated with alveolar inflammation as measured by an increased concentration of alveolar nitric oxide (r = 0.76, p = 0.003). CONCLUSIONS: Blood eosinophils change phenotype during disease evolution in SSc, and CD48 expression may be used as a biomarker for pulmonary inflammation.
[Mh] Termos MeSH primário: Antígenos CD/metabolismo
Eosinófilos/metabolismo
Fibrose Pulmonar/metabolismo
Escleroderma Sistêmico/metabolismo
Tetraspanina 28/metabolismo
[Mh] Termos MeSH secundário: Idoso
Biomarcadores
Antígeno CD48
Estudos de Casos e Controles
Citometria de Fluxo
Seres Humanos
Masculino
Meia-Idade
Óxido Nítrico/metabolismo
Fenótipo
Fibrose Pulmonar/etiologia
Esclerodermia Difusa/metabolismo
Esclerodermia Limitada/metabolismo
Escleroderma Sistêmico/complicações
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antigens, CD); 0 (Biomarkers); 0 (CD48 Antigen); 0 (CD48 protein, human); 0 (CD81 protein, human); 0 (Tetraspanin 28); 31C4KY9ESH (Nitric Oxide)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160302
[St] Status:MEDLINE
[do] DOI:10.3109/03009742.2015.1054877


  5 / 258 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26794910
[Au] Autor:McArdel SL; Terhorst C; Sharpe AH
[Ad] Endereço:Department of Microbiology and Immunobiology, Evergrande Center for Immunologic Diseases, Harvard Medical School, Boston, MA, USA.
[Ti] Título:Roles of CD48 in regulating immunity and tolerance.
[So] Source:Clin Immunol;164:10-20, 2016 Mar.
[Is] ISSN:1521-7035
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:CD48, a member of the signaling lymphocyte activation molecule family, participates in adhesion and activation of immune cells. Although constitutively expressed on most hematopoietic cells, CD48 is upregulated on subsets of activated cells. CD48 can have activating roles on T cells, antigen presenting cells and granulocytes, by binding to CD2 or bacterial FimH, and through cell intrinsic effects. Interactions between CD48 and its high affinity ligand CD244 are more complex, with both stimulatory and inhibitory outcomes. CD244:CD48 interactions regulate target cell lysis by NK cells and CTLs, which are important for viral clearance and regulation of effector/memory T cell generation and survival. Here we review roles of CD48 in infection, tolerance, autoimmunity, and allergy, as well as the tools used to investigate this receptor. We discuss stimulatory and regulatory roles for CD48, its potential as a therapeutic target in human disease, and current challenges to investigation of this immunoregulatory receptor.
[Mh] Termos MeSH primário: Antígenos CD/imunologia
[Mh] Termos MeSH secundário: Animais
Autoimunidade
Antígeno CD48
Antígenos CD58/imunologia
Seres Humanos
Tolerância Imunológica
Ligantes
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; REVIEW
[Nm] Nome de substância:
0 (Antigens, CD); 0 (CD48 Antigen); 0 (CD48 protein, human); 0 (CD58 Antigens); 0 (Ligands)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160123
[St] Status:MEDLINE


  6 / 258 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26683280
[Au] Autor:Revollo JR; Crabtree NM; Pearce MG; Pacheco-Martinez MM; Dobrovolsky VN
[Ad] Endereço:Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas.
[Ti] Título:Mutation analysis with random DNA identifiers (MARDI) catalogs Pig-a mutations in heterogeneous pools of CD48-deficient T cells derived from DMBA-treated rats.
[So] Source:Environ Mol Mutagen;57(2):114-24, 2016 Mar.
[Is] ISSN:1098-2280
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Identification of mutations induced by xenotoxins is a common task in the field of genetic toxicology. Mutations are often detected by clonally expanding potential mutant cells and genotyping each viable clone by Sanger sequencing. Such a "clone-by-clone" approach requires significant time and effort, and sometimes is even impossible to implement. Alternative techniques for efficient mutation identification would greatly benefit both basic and regulatory genetic toxicology research. Here, we report the development of Mutation Analysis with Random DNA Identifiers (MARDI), a novel high-fidelity Next Generation Sequencing (NGS) approach that circumvents clonal expansion and directly catalogs mutations in pools of mutant cells. MARDI uses oligonucleotides carrying Random DNA Identifiers (RDIs) to tag progenitor DNA molecules before PCR amplification, enabling clustering of descendant DNA molecules and eliminating NGS- and PCR-induced sequencing artifacts. When applied to the Pig-a cDNA analysis of heterogeneous pools of CD48-deficient T cells derived from DMBA-treated rats, MARDI detected nearly all Pig-a mutations that were previously identified by conventional clone-by-clone analysis and discovered many additional ones consistent with DMBA exposure: mostly A to T transversions, with the mutated A located on the non-transcribed DNA strand.
[Mh] Termos MeSH primário: 9,10-Dimetil-1,2-benzantraceno/toxicidade
Análise Mutacional de DNA/métodos
Mutação
Linfócitos T/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Antígenos CD/genética
Antígenos CD/metabolismo
Antígeno CD48
Sequenciamento de Nucleotídeos em Larga Escala/métodos
Masculino
Reação em Cadeia da Polimerase/métodos
Ratos Endogâmicos F344
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD); 0 (CD48 Antigen); 0 (Cd48 protein, rat); 57-97-6 (9,10-Dimethyl-1,2-benzanthracene)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:161126
[Lr] Data última revisão:
161126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151220
[St] Status:MEDLINE
[do] DOI:10.1002/em.21992


  7 / 258 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26314831
[Au] Autor:Kis-Toth K; Comte D; Karampetsou MP; Kyttaris VC; Kannan L; Terhorst C; Tsokos GC
[Ad] Endereço:Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
[Ti] Título:Selective Loss of Signaling Lymphocytic Activation Molecule Family Member 4-Positive CD8+ T Cells Contributes to the Decreased Cytotoxic Cell Activity in Systemic Lupus Erythematosus.
[So] Source:Arthritis Rheumatol;68(1):164-73, 2016 Jan.
[Is] ISSN:2326-5205
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Engagement of signaling lymphocytic activation molecule family member 4 (SLAMF4; CD244, 2B4) by its ligand SLAMF2 (CD48) modulates the function and expansion of both natural killer cells and a subset of cytotoxic CD8+ T cells. Because the cytotoxicity of CD8+ T lymphocytes isolated from patients with systemic lupus erythematosus (SLE) is known to be impaired, the aim of this study was to assess whether the expression and function of the checkpoint regulator SLAMF4 are altered on CD8+ T cells from patients with SLE. METHODS: The expression of SLAMF4 by T cells from healthy donors and patients with SLE was determined by quantitative polymerase chain reaction and flow cytometry. T cells were activated with anti-CD3 antibody, and degranulation activity was monitored by the surface expression of lysosome-associated membrane protein 1 (LAMP-1; CD107a). The SLAMF4+ and SLAMF4- CD8+ T cell subpopulations were characterized by LAMP-1, perforin, and granzyme B expression and viral peptide-induced proliferation. RESULTS: SLAMF4 gene and surface protein expression was down-regulated in CD8+ T cells from SLE patients compared with that in cells obtained from healthy donors. Importantly, SLE patients had significantly fewer SLAMF4+ CD8+ T cells compared with healthy donors. SLAMF4- CD8+ T cells from SLE patients had a decreased cytotoxic capacity and decreased proliferative responses to viral peptides. The loss of memory SLAMF4+ CD8+ T cells in SLE patients was linked to the fact that these cells have an increased propensity to lose CD8 expression and become double-negative T cells. CONCLUSION: A selective loss of SLAMF4+ CD8+ T cells contributes to the compromised ability of T cells from patients with SLE to fight infection.
[Mh] Termos MeSH primário: Antígenos CD/imunologia
Lúpus Eritematoso Sistêmico/imunologia
RNA Mensageiro/metabolismo
Receptores Imunológicos/imunologia
Linfócitos T Citotóxicos/imunologia
[Mh] Termos MeSH secundário: Antígenos CD/genética
Western Blotting
Antígeno CD48
Linfócitos T CD8-Positivos/imunologia
Linfócitos T CD8-Positivos/metabolismo
Estudos de Casos e Controles
Proliferação Celular
Citometria de Fluxo
Expressão Gênica
Granzimas/metabolismo
Seres Humanos
Células Matadoras Naturais/imunologia
Lúpus Eritematoso Sistêmico/genética
Ativação Linfocitária
Perforina/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
Receptores Imunológicos/genética
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Família de Moléculas de Sinalização da Ativação Linfocitária
Linfócitos T Citotóxicos/metabolismo
Proteínas Virais
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Antigens, CD); 0 (CD244 protein, human); 0 (CD48 Antigen); 0 (CD48 protein, human); 0 (RNA, Messenger); 0 (Receptors, Immunologic); 0 (Signaling Lymphocytic Activation Molecule Family); 0 (Viral Proteins); 126465-35-8 (Perforin); EC 3.4.21.- (Granzymes)
[Em] Mês de entrada:1605
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:150829
[St] Status:MEDLINE
[do] DOI:10.1002/art.39410


  8 / 258 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:26339044
[Au] Autor:Pérez-Carmona N; Farré D; Martínez-Vicente P; Terhorst C; Engel P; Angulo A
[Ad] Endereço:Immunology Unit, Department of Cell Biology, Immunology, and Neurosciences, Medical School, University of Barcelona, Barcelona, Spain.
[Ti] Título:Signaling Lymphocytic Activation Molecule Family Receptor Homologs in New World Monkey Cytomegaloviruses.
[So] Source:J Virol;89(22):11323-36, 2015 Nov.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:UNLABELLED: Throughout evolution, large DNA viruses have been usurping genes from their hosts to equip themselves with proteins that restrain host immune defenses. Signaling lymphocytic activation molecule (SLAM) family (SLAMF) receptors are involved in the regulation of both innate and adaptive immunity, which occurs upon engagement with their ligands via homotypic or heterotypic interactions. Here we report a total of seven SLAMF genes encoded by the genomes of two cytomegalovirus (CMV) species, squirrel monkey CMV (SMCMV) and owl monkey CMV (OMCMV), that infect New World monkeys. Our results indicate that host genes were captured by retrotranscription at different stages of the CMV-host coevolution. The most recent acquisition led to S1 in SMCMV. S1 is a SLAMF6 homolog with an amino acid sequence identity of 97% to SLAMF6 in its ligand-binding N-terminal Ig domain. We demonstrate that S1 is a cell surface glycoprotein capable of binding to host SLAMF6. Furthermore, the OMCMV genome encodes A33, an LY9 (SLAMF3) homolog, and A43, a CD48 (SLAMF2) homolog, two soluble glycoproteins which recognize their respective cellular counterreceptors and thus are likely to be viral SLAMF decoy receptors. In addition, distinct copies of further divergent CD48 homologs were found to be encoded by both CMV genomes. Remarkably, all these molecules display a number of unique features, including cytoplasmic tails lacking characteristic SLAMF signaling motifs. Taken together, our findings indicate a novel immune evasion mechanism in which incorporation of host SLAMF receptors that retain their ligand-binding properties enables viruses to interfere with SLAMF functions and to supply themselves with convenient structural molds for expanding their immunomodulatory repertoires. IMPORTANCE: The way in which viruses shape their genomes under the continual selective pressure exerted by the host immune system is central for their survival. Here, we report that New World monkey cytomegaloviruses have broadly captured and duplicated immune cell receptors of the signaling lymphocyte activation molecule (SLAM) family during host-virus coevolution. Notably, we demonstrate that several of these viral SLAMs exhibit exceptional preservation of their N-terminal immunoglobulin domains, which results in maintenance of their ligand-binding capacities. At the same time, these molecules present distinctive structural properties which include soluble forms and the absence of typical SLAM signaling motifs in their cytoplasmic domains, likely reflecting the evolutionary adaptation undergone to efficiently interfere with host SLAM family activities. The observation that the genomes of other large DNA viruses might bear SLAM family homologs further underscores the importance of these molecules as a novel class of immune regulators and as convenient scaffolds for viral evolution.
[Mh] Termos MeSH primário: Antígenos CD/imunologia
Aotidae/virologia
Citomegalovirus/imunologia
Ativação Linfocitária/imunologia
Receptores de Superfície Celular/imunologia
Saimiri/virologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Antígenos CD/genética
Antígenos CD/metabolismo
Antígeno CD48
Infecções por Citomegalovirus/imunologia
Infecções por Citomegalovirus/veterinária
Infecções por Citomegalovirus/virologia
Expressão Gênica/genética
Regulação da Expressão Gênica/fisiologia
Linfócitos/imunologia
Glicoproteínas de Membrana/metabolismo
Receptores de Superfície Celular/genética
Receptores de Superfície Celular/metabolismo
Transdução de Sinais/imunologia
Membro 1 da Família de Moléculas de Sinalização da Ativação Linfocitária
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antigens, CD); 0 (CD48 Antigen); 0 (Membrane Glycoproteins); 0 (Receptors, Cell Surface); 169535-43-7 (Signaling Lymphocytic Activation Molecule Family Member 1)
[Em] Mês de entrada:1601
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150905
[St] Status:MEDLINE
[do] DOI:10.1128/JVI.01296-15


  9 / 258 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26033714
[Au] Autor:Dobrovolsky VN; Revollo J; Pearce MG; Pacheco-Martinez MM; Lin H
[Ad] Endereço:Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas.
[Ti] Título:CD48-deficient T-lymphocytes from DMBA-treated rats have de novo mutations in the endogenous Pig-a gene.
[So] Source:Environ Mol Mutagen;56(8):674-83, 2015 Oct.
[Is] ISSN:1098-2280
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A major question concerning the scientific and regulatory acceptance of the rodent red blood cell-based Pig-a gene mutation assay is the extent to which mutants identified by their phenotype in the assay are caused by mutations in the Pig-a gene. In this study, we identified T-lymphocytes deficient for the glycosylphosphatidylinositol-anchored surface marker, CD48, in control and 7,12-dimethylbenz[a]anthracene (DMBA)-treated rats using a flow cytometric assay and determined the spectra of mutations in the endogenous Pig-a gene in these cells. CD48-deficient T-cells were seeded by sorting at one cell per well into 96-well plates, expanded into clones, and exons of their genomic Pig-a were sequenced. The majority (78%) of CD48-deficient T-cell clones from DMBA-treated rats had mutations in the Pig-a gene. The spectrum of DMBA-induced Pig-a mutations was dominated by mutations at A:T, with the mutated A being on the nontranscribed strand and A → T transversion being the most frequent change. The spectrum of Pig-a mutations in DMBA-treated rats was different from the spectrum of Pig-a mutations in N-ethyl-N-nitrosourea (ENU)-treated rats, but similar to the spectrum of DMBA mutations for another endogenous X-linked gene, Hprt. Only 15% of CD48-deficient mutants from control animals contained Pig-a mutations; T-cell biology may be responsible for a relatively large fraction of false Pig-a mutant lymphocytes in control animals. Among the verified mutants from control rats, the most common were frameshifts and deletions. The differences in the spectra of spontaneous, DMBA-, and ENU-induced Pig-a mutations suggest that the flow cytometric Pig-a assay detects de novo mutation in the endogenous Pig-a gene.
[Mh] Termos MeSH primário: 9,10-Dimetil-1,2-benzantraceno/toxicidade
Antígenos CD/metabolismo
Proteínas de Membrana/genética
Mutação
Linfócitos T/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Antígenos CD/genética
Antígeno CD48
Citometria de Fluxo
Masculino
Proteínas de Membrana/metabolismo
Testes de Mutagenicidade
Mutagênicos/toxicidade
Ratos Endogâmicos F344
Linfócitos T/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antigens, CD); 0 (CD48 Antigen); 0 (Cd48 protein, rat); 0 (Membrane Proteins); 0 (Mutagens); 0 (phosphatidylinositol glycan-class A protein); 57-97-6 (9,10-Dimethyl-1,2-benzanthracene)
[Em] Mês de entrada:1604
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150603
[St] Status:MEDLINE
[do] DOI:10.1002/em.21959


  10 / 258 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:25820172
[Au] Autor:Revollo J; Pearce MG; Petibone DM; Mittelstaedt RA; Dobrovolsky VN
[Ad] Endereço:Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA.
[Ti] Título:Confirmation of Pig-a mutation in flow cytometry-identified CD48-deficient T-lymphocytes from F344 rats.
[So] Source:Mutagenesis;30(3):315-24, 2015 May.
[Is] ISSN:1464-3804
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The Pig-a assay is used for monitoring somatic cell mutation in laboratory animals and humans. The assay detects haematopoietic cells deficient in glycosylphosphatidylinositol (GPI)-anchored protein surface markers using flow cytometry. However, given that synthesis of the protein markers (and the expression of their genes) is independent of the expression of the X-linked Pig-a gene and the function of its enzyme product, the deficiency of markers at the surface of the cells may be caused by a number of events (e.g. by mutation or epigenetic silencing in the marker gene itself or in any of about two dozen autosomal genes involved in the synthesis of GPI). Here we provide direct evidence that the deficiency of the GPI-anchored surface marker CD48 in rat T-cells is accompanied by mutation in the endogenous X-linked Pig-a gene. We treated male F344 rats with N-ethyl-N-nitrosourea (ENU), and established colonies from flow cytometry-identified and sorted CD48-deficient spleen T-lymphocytes. Molecular analysis confirmed that the expanded sorted cells have mutations in the Pig-a gene. The spectrum of Pig-a mutation in our model was consistent with the spectrum of ENU-induced mutation determined in other in vivo models, mostly base-pair substitutions at A:T with the mutated T on the non-transcribed strand of Pig-a genomic DNA. We also used next generation sequencing to derive a similar mutational spectrum from a pool of 64 clones developed from flow-sorted CD48-deficient lymphocytes. Our findings confirm that Pig-a assays detect what they are designed to detect-gene mutation in the Pig-a gene.
[Mh] Termos MeSH primário: Proteínas de Membrana/genética
Linfócitos T/metabolismo
[Mh] Termos MeSH secundário: Animais
Antígenos CD/genética
Antígenos CD/metabolismo
Sequência de Bases
Antígeno CD48
Células Cultivadas
Análise Mutacional de DNA
Etilnitrosoureia/farmacologia
Citometria de Fluxo
Sequenciamento de Nucleotídeos em Larga Escala
Separação Imunomagnética
Masculino
Mutagênese
Testes de Mutagenicidade
Mutagênicos/farmacologia
Mutação
Fenótipo
Ratos Endogâmicos F344
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD); 0 (CD48 Antigen); 0 (CD48 protein, human); 0 (Cd48 protein, rat); 0 (Membrane Proteins); 0 (Mutagens); 0 (phosphatidylinositol glycan-class A protein); P8M1T4190R (Ethylnitrosourea)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150331
[St] Status:MEDLINE
[do] DOI:10.1093/mutage/geu030



página 1 de 26 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde