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Pesquisa : A11.118.637.555.567.550.500.400 [Categoria DeCS]
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  1 / 13709 MEDLINE  
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[PMID]:28453219
[Au] Autor:Worsham DN; Reems JA; Szczepiorkowski ZM; McKenna DH; Leemhuis T; Mathew AJ; Cancelas JA; Biomedical Excellence for Safer Transfusion (BEST) Collaborative Group
[Ad] Endereço:Hoxworth Blood Center, University of Cincinnati, Cincinnati, Ohio.
[Ti] Título:Clinical methods of cryopreservation for donor lymphocyte infusions vary in their ability to preserve functional T-cell subpopulations.
[So] Source:Transfusion;57(6):1555-1565, 2017 06.
[Is] ISSN:1537-2995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Cryopreserved donor lymphocyte infusion (DLI) products are manufactured and administered to treat relapse after allogeneic hematopoietic stem cell transplantation. Reported clinical responses to DLIs vary broadly, even within the same group of patients. While there is an implicit recognition of the fact that different manufacturing protocols may have specific effects on different cell types, cryopreservation protocols are frequently derived from our experience in the cryopreservation of stem cell products and do not account for the heterogeneous functional nature of DLI T-cell populations. Here, we report the results of a prospective, multicenter trial on the effect of four different cryopreservation solutions that were used to freeze DLIs compared to control DLIs that were refrigerated overnight. STUDY DESIGN AND METHODS: Cryopreserved postthawed and refrigerated specimens were analyzed side by side for their T-cell subpopulation content and viability, as well as T-cell proliferation, cytokine secretion, and cytotoxic activities. RESULTS: This study indicates that "homemade" 10% dimethyl sulfoxide (DMSO) results in reduced viability of different CD4+ T-cell populations, including T-helper, T-cytotoxic, and T-regulatory populations, and a decrease in their proliferative and cytotoxic response to immunologically relevant stimuli, while the use of solutions containing 5% DMSO with intracellular-like cryoprotectant stabilizers maintains T-cell function at levels similar to refrigerated control samples. CONCLUSION: This study has important implications in determining the best cryoprotectant solution for specific clinical applications in allogeneic immunotherapy.
[Mh] Termos MeSH primário: Criopreservação/métodos
Transfusão de Linfócitos/métodos
[Mh] Termos MeSH secundário: Linfócitos T CD4-Positivos/citologia
Linfócitos T CD4-Positivos/imunologia
Ciclo Celular/fisiologia
Dimetil Sulfóxido/química
Transplante de Células-Tronco Hematopoéticas
Seres Humanos
Imunofenotipagem
Linfócitos T Citotóxicos/citologia
Linfócitos T Citotóxicos/imunologia
Linfócitos T Auxiliares-Indutores/citologia
Linfócitos T Auxiliares-Indutores/imunologia
Linfócitos T Reguladores/citologia
Linfócitos T Reguladores/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
YOW8V9698H (Dimethyl Sulfoxide)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1111/trf.14112


  2 / 13709 MEDLINE  
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[PMID]:29386429
[Au] Autor:Uno K
[Ad] Endereço:Faculty of Pharmacy, Chiba Institute of Science.
[Ti] Título:[Pathogenic Mechanism and Diagnostic Testing for Drug Allergies].
[So] Source:Yakugaku Zasshi;138(2):151-167, 2018.
[Is] ISSN:1347-5231
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo: Three stages of the pathogenic mechanism of drug allergies can be considered: antigen formation, immune reaction and inflammation/disorder reaction. Drugs are thought to form 4 types of antigens: drug only, polymers, drug-carrier conjugates, and metabolite-carrier complexes. Antigens are recognized by B cell receptors and T cell receptors. Helper T cells (Th) are differentiated into four subsets, namely, Th1, Th2, Th17 and regulatory T cells (Treg). Th1 produces interleukin (IL)-2 and interferon (IFN)-γ, and activates macrophages and cytotoxic T cells (Tc). Macrophages induce type IV allergies, and Tc lead to serious type IV allergies. On the other hand, Th2 produces IL-4, IL-5, and IL-6, etc., and activates B cells. B cells produce IgE antibodies, and the IgE antibody affects mast cells and induces type I allergies. Activated eosinophil leads to the chronic state of type I allergy. Diagnostic testing for allergenic drugs is necessary for patients with drug allergies. Because in vivo diagnostic tests for allergenic drugs are associated with a risk and burden to the patient, in vitro allergy tests are recommended to identify allergenic drugs. In allergy tests performed in vitro, cytological tests are more effective than serological tests, and the leukocyte migration test (LMT) presently has the highest efficacy. An LMT-chamber is better than LMT-agarose in terms of usability and sensitivity, and it can detect about 80% of allergenic drugs.
[Mh] Termos MeSH primário: Ensaios de Migração de Leucócitos
Hipersensibilidade a Drogas/diagnóstico
Hipersensibilidade a Drogas/imunologia
[Mh] Termos MeSH secundário: Antígenos/imunologia
Linfócitos B/imunologia
Citocinas/metabolismo
Eosinófilos/imunologia
Seres Humanos
Imunoglobulina E
Macrófagos/imunologia
Mastócitos/imunologia
Receptores de Antígenos de Linfócitos B/imunologia
Receptores de Antígenos de Linfócitos T/imunologia
Sensibilidade e Especificidade
Subpopulações de Linfócitos T/imunologia
Linfócitos T Auxiliares-Indutores/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antigens); 0 (Cytokines); 0 (Receptors, Antigen, B-Cell); 0 (Receptors, Antigen, T-Cell); 37341-29-0 (Immunoglobulin E)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180202
[St] Status:MEDLINE
[do] DOI:10.1248/yakushi.17-00174-1


  3 / 13709 MEDLINE  
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[PMID]:29388830
[Au] Autor:de Jong E; Bosco A
[Ad] Endereço:1 Telethon Kids Institute University of Western Australia Subiaco, Australia.
[Ti] Título:Dissecting Asthma Transcriptomics: Does Site Matter?
[So] Source:Am J Respir Cell Mol Biol;58(2):144-146, 2018 02.
[Is] ISSN:1535-4989
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Corticosteroides/uso terapêutico
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico
Antiasmáticos/uso terapêutico
Asma/tratamento farmacológico
Asma/patologia
Transcriptoma/genética
[Mh] Termos MeSH secundário: Asma/genética
Perfilação da Expressão Gênica
Seres Humanos
Linfócitos T Auxiliares-Indutores/imunologia
[Pt] Tipo de publicação:EDITORIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adrenal Cortex Hormones); 0 (Adrenergic beta-2 Receptor Agonists); 0 (Anti-Asthmatic Agents)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180202
[St] Status:MEDLINE
[do] DOI:10.1165/rcmb.2017-0360ED


  4 / 13709 MEDLINE  
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[PMID]:27770341
[Au] Autor:Sierzega M; Lenart M; Rutkowska M; Surman M; Mytar B; Matyja A; Siedlar M; Kulig J
[Ad] Endereço:First Department of General and GI Surgery, Jagiellonian University Medical College, Krakow, Poland. marek.sierzega@uj.edu.pl.
[Ti] Título:Preoperative Neutrophil-Lymphocyte and Lymphocyte-Monocyte Ratios Reflect Immune Cell Population Rearrangement in Resectable Pancreatic Cancer.
[So] Source:Ann Surg Oncol;24(3):808-815, 2017 Mar.
[Is] ISSN:1534-4681
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR) may serve as a simple index of the immune function. The aim of this study was to investigate the prognostic significance of NLR, PLR, and LMR in patients with resectable pancreatic ductal adenocarcinoma (PDAC) and to verify whether such biomarkers are associated with changes in populations of lymphoid cells. METHODS: The prognostic implications of blood count parameters were evaluated in a retrospective cohort of 442 subjects undergoing pancreatic resections for PDAC. Subpopulations of lymphocytes and monocytes in peripheral blood were identified by FACS in a prospective cohort of 54 patients. RESULTS: In the univariate analysis, NLR < 5 and LMR ≥ 3 were associated with significantly longer median survival of 25.7 vs 12.6 months and 29.2 vs 13.1 months, respectively. PLR did not influence survival. The Cox proportional hazards model showed that high NLR (HR 1.66, 95 % CI 1.12 to 2.46, P = 0.012) and low LMR (HR 1.65, 95 % CI 1.06 to 2.58, P = 0.026) were independent predictors of poor prognosis. NLR ≥ 5 and LMR < 3 correlated with an approximately twofold decrease in counts of helper and cytotoxic T cells, B cells, and NK cells. High NLR was also accompanied with increased neutrophil counts, while low LMR showed increased numbers of monocytes, mostly classical. CONCLUSIONS: NLR and LMR may carry important prognostic information for patients with resected PDAC. The unfavorable prognosis likely correlates with reduced numbers of immune cells effective against the tumor and increased populations of cells involved in immune suppression.
[Mh] Termos MeSH primário: Carcinoma Ductal Pancreático/sangue
Linfócitos
Monócitos
Neutrófilos
Neoplasias Pancreáticas/sangue
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Linfócitos B
Biomarcadores Tumorais/sangue
Carcinoma Ductal Pancreático/imunologia
Carcinoma Ductal Pancreático/cirurgia
Feminino
Seres Humanos
Células Matadoras Naturais
Contagem de Linfócitos
Masculino
Meia-Idade
Neoplasias Pancreáticas/imunologia
Neoplasias Pancreáticas/cirurgia
Contagem de Plaquetas
Prognóstico
Estudos Prospectivos
Estudos Retrospectivos
Taxa de Sobrevida
Linfócitos T Citotóxicos
Linfócitos T Auxiliares-Indutores
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161023
[St] Status:MEDLINE
[do] DOI:10.1245/s10434-016-5634-0


  5 / 13709 MEDLINE  
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[PMID]:29293620
[Au] Autor:Byford ET; Carr M; Ladikou E; Ahearne MJ; Wagner SD
[Ad] Endereço:Leicester Cancer Research Centre and Ernest and Helen Scott Haematology Research Institute, University of Leicester, Leicester, United Kingdom.
[Ti] Título:Circulating Tfh1 (cTfh1) cell numbers and PD1 expression are elevated in low-grade B-cell non-Hodgkin's lymphoma and cTfh gene expression is perturbed in marginal zone lymphoma.
[So] Source:PLoS One;13(1):e0190468, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:CD4+ T-cell subsets are found in the tumour microenvironment (TME) of low-grade B-cell non-Hodgkin's lymphomas such as marginal zone lymphoma (MZL) or follicular lymphoma (FL). Both numbers and architecture of activating follicular helper T-cells (Tfh) and suppressive Treg in the TME of FL are associated with clinical outcomes. There has been almost no previous work on CD4+ T-cells in MZL. It is now recognised that circulating CD4+CXCR5+ T-cells are the memory compartment of Tfh cells. We determined differences in number of circulating Tfh (cTfh) cells and cTfh subsets between normal subjects and patients with FL or MZL. Lymphoma patients showed increased numbers of cTfh1 and reduced cTfh17 cells due to decreased expression of the subset-defining marker CCR6 in patients. PD1, a surface marker associated with Tfh cells, showed increased expression on cTfh subsets in patients. Focusing on MZL we determined expression of 96 T-cell associated genes by microfluidic qRT-PCR. Analysis of differentially expressed genes showed significant differences between normal subjects and patients both for bulk cTfh (CCL4) and the cTfh1 subset (JAK3). While our findings require confirmation in larger studies we suggest that analysis of number and gene expression of circulating T-cells might be a source of clinically useful information as is the case for T-cells within lymphoma lymph nodes.
[Mh] Termos MeSH primário: Linfoma de Zona Marginal Tipo Células B/genética
Receptor de Morte Celular Programada 1/genética
Linfócitos T Auxiliares-Indutores/metabolismo
Linfócitos T Reguladores/metabolismo
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Estudos de Casos e Controles
Feminino
Citometria de Fluxo
Expressão Gênica
Seres Humanos
Masculino
Meia-Idade
Reação em Cadeia da Polimerase em Tempo Real
Linfócitos T Auxiliares-Indutores/citologia
Linfócitos T Reguladores/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (PDCD1 protein, human); 0 (Programmed Cell Death 1 Receptor)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180103
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190468


  6 / 13709 MEDLINE  
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[PMID]:29223395
[Au] Autor:Takebe T; Sakamoto K; Higami Y; Harada Y
[Ad] Endereço:Laboratory of Pharmaceutical Immunology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan; Laboratory of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba,
[Ti] Título:A novel mouse model for tracking the fate of CXCR5-expressing T cells.
[So] Source:Biochem Biophys Res Commun;495(2):1642-1647, 2018 01 08.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The germinal center (GC) reaction, a critical process in the humoral immune response, requires follicular helper T (Tfh) cells. Tfh cells express the master transcription factor Bcl6 and chemokine receptor CXCR5, which enable them to migrate from the T cell zone to B cell follicles and interact with GC B cells. However, CXCR5 is downregulated when Tfh cells become memory cells. Therefore, it is difficult to track Tfh cells continuously in vivo. In this study, we generated a mouse strain, Cxcr5 R26 , in which the fluorescent protein tdTomato is inducibly expressed in CXCR5 cells by tamoxifen administration. After the oral administration of tamoxifen, most Tfh cells in Peyer's patches (PP) from Cxcr5 R26 mice were tdTomato . To track antigen-specific Tfh cells in vivo, OVA-specific OT-II T cells derived from Cxcr5 R26 mice were transferred to wild-type mice, and the recipient mice were immunized with OVA followed by tamoxifen administration. CXCR5 T cells became tdTomato and were mainly located in B cell follicles and GC areas 8 days after immunization. Four weeks after immunization, tdTomato OT-II T cells migrated from B cell follicles to the T-B border area and T cell zone after CXCR5 downregulation and CCR7 upregulation. These results indicate that Cxcr5 R26 mice are a useful tool for studying the cell fate of differentiated Tfh cells in vivo and therefore have implications for the development of therapeutic strategies for infectious and autoimmune diseases.
[Mh] Termos MeSH primário: Receptores CXCR5/metabolismo
Linfócitos T Auxiliares-Indutores/imunologia
[Mh] Termos MeSH secundário: Transferência Adotiva
Animais
Linfócitos B/imunologia
Diferenciação Celular
Movimento Celular/imunologia
Centro Germinativo/citologia
Centro Germinativo/imunologia
Imunidade Humoral
Memória Imunológica
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Modelos Animais
Modelos Imunológicos
Ovalbumina/imunologia
Receptores CXCR5/genética
Linfócitos T Auxiliares-Indutores/citologia
Linfócitos T Auxiliares-Indutores/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Blr1 protein, mouse); 0 (Receptors, CXCR5); 9006-59-1 (Ovalbumin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171211
[St] Status:MEDLINE


  7 / 13709 MEDLINE  
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[PMID]:28467912
[Au] Autor:Yan H; Wu L; Shih C; Hou S; Shi J; Mao T; Chen W; Melvin B; Rigby RJ; Chen Y; Jiang H; Friedel RH; Vinuesa CG; Qi H
[Ad] Endereço:Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China; Laboratory of Dynamic Immunobiology, Institute for Immunology, Tsinghua University, Beijing 100084, China; Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
[Ti] Título:Plexin B2 and Semaphorin 4C Guide T Cell Recruitment and Function in the Germinal Center.
[So] Source:Cell Rep;19(5):995-1007, 2017 May 02.
[Is] ISSN:2211-1247
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Follicular T helper (T ) cells orchestrate the germinal center (GC) response locally. T localization in GCs is controlled by chemo-guidance cues and antigen-specific adhesion. Here. we define an antigen-independent, contact-dependent, adhesive guidance system for T cells. Unusual for amoeboid cell migration, the system is composed of transmembrane plexin B2 (PlxnB2) molecule, which is highly expressed by GC B cells, and its transmembrane binding partner semaphorin 4C (Sema4C), which is upregulated on T cells. Sema4C on T cells serves as a receptor to sense the GC-presented PlxnB2 cue and biases T migration inwards at the GC edge to promote GC access. The absence of PlxnB2 from the GC or Sema4C from T cells causes T accumulation along the GC border, impairs T-B cell interactions in the GC, and is associated with defective plasma cell production and affinity maturation. Therefore, Sema4C and PlxnB2 regulate GC T recruitment and function and optimize antibody responses.
[Mh] Termos MeSH primário: Movimento Celular
Centro Germinativo/citologia
Proteínas do Tecido Nervoso/metabolismo
Semaforinas/metabolismo
Linfócitos T Auxiliares-Indutores/metabolismo
[Mh] Termos MeSH secundário: Animais
Linfócitos B/fisiologia
Células Cultivadas
Centro Germinativo/metabolismo
Camundongos
Linfócitos T Auxiliares-Indutores/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Nerve Tissue Proteins); 0 (Sema4c protein, mouse); 0 (Semaphorins); 0 (plexin B2 protein, mouse)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE


  8 / 13709 MEDLINE  
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[PMID]:29180490
[Au] Autor:Kunicki MA; Amaya Hernandez LC; Davis KL; Bacchetta R; Roncarolo MG
[Ad] Endereço:Division of Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University, Stanford, CA 94305.
[Ti] Título:Identity and Diversity of Human Peripheral Th and T Regulatory Cells Defined by Single-Cell Mass Cytometry.
[So] Source:J Immunol;200(1):336-346, 2018 01 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human CD3 CD4 Th cells, FOXP3 T regulatory (Treg) cells, and T regulatory type 1 (Tr1) cells are essential for ensuring peripheral immune response and tolerance, but the diversity of Th, Treg, and Tr1 cell subsets has not been fully characterized. Independent functional characterization of human Th1, Th2, Th17, T follicular helper (Tfh), Treg, and Tr1 cells has helped to define unique surface molecules, transcription factors, and signaling profiles for each subset. However, the adequacy of these markers to recapitulate the whole CD3 CD4 T cell compartment remains questionable. In this study, we examined CD3 CD4 T cell populations by single-cell mass cytometry. We characterize the CD3 CD4 Th, Treg, and Tr1 cell populations simultaneously across 23 memory T cell-associated surface and intracellular molecules. High-dimensional analysis identified several new subsets, in addition to the already defined CD3 CD4 Th, Treg, and Tr1 cell populations, for a total of 11 Th cell, 4 Treg, and 1 Tr1 cell subsets. Some of these subsets share markers previously thought to be selective for Treg, Th1, Th2, Th17, and Tfh cells, including CD194 (CCR4) FOXP3 Treg and CD183 (CXCR3) T-bet Th17 cell subsets. Unsupervised clustering displayed a phenotypic organization of CD3 CD4 T cells that confirmed their diversity but showed interrelation between the different subsets, including similarity between Th1-Th2-Tfh cell populations and Th17 cells, as well as similarity of Th2 cells with Treg cells. In conclusion, the use of single-cell mass cytometry provides a systems-level characterization of CD3 CD4 T cells in healthy human blood, which represents an important baseline reference to investigate abnormalities of different subsets in immune-mediated pathologies.
[Mh] Termos MeSH primário: Subpopulações de Linfócitos T/imunologia
Linfócitos T Auxiliares-Indutores/imunologia
Linfócitos T Reguladores/imunologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Biodiversidade
Feminino
Fatores de Transcrição Forkhead/metabolismo
Homeostase
Seres Humanos
Tolerância Imunológica
Masculino
Espectrometria de Massas/métodos
Meia-Idade
Análise de Célula Única
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (FOXP3 protein, human); 0 (Forkhead Transcription Factors)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180131
[Lr] Data última revisão:
180131
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171129
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1701025


  9 / 13709 MEDLINE  
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[PMID]:29186193
[Au] Autor:Sprokholt JK; Kaptein TM; van Hamme JL; Overmars RJ; Gringhuis SI; Geijtenbeek TBH
[Ad] Endereço:Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
[Ti] Título:RIG-I-like receptor activation by dengue virus drives follicular T helper cell formation and antibody production.
[So] Source:PLoS Pathog;13(11):e1006738, 2017 Nov.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Follicular T helper cells (TFH) are fundamental in orchestrating effective antibody-mediated responses critical for immunity against viral infections and effective vaccines. However, it is unclear how virus infection leads to TFH induction. We here show that dengue virus (DENV) infection of human dendritic cells (DCs) drives TFH formation via crosstalk of RIG-I-like receptor (RLR) RIG-I and MDA5 with type I Interferon (IFN) signaling. DENV infection leads to RLR-dependent IKKε activation, which phosphorylates IFNα/ß receptor-induced STAT1 to drive IL-27 production via the transcriptional complex ISGF3. Inhibiting RLR activation as well as neutralizing antibodies against IL-27 prevented TFH formation. DENV-induced CXCR5+PD-1+Bcl-6+ TFH cells secreted IL-21 and activated B cells to produce IgM and IgG. Notably, RLR activation by synthetic ligands also induced IL-27 secretion and TFH polarization. These results identify an innate mechanism by which antibodies develop during viral disease and identify RLR ligands as potent adjuvants for TFH-promoting vaccination strategies.
[Mh] Termos MeSH primário: Anticorpos Antivirais/imunologia
Vírus da Dengue/fisiologia
Dengue/imunologia
Linfócitos T Auxiliares-Indutores/imunologia
[Mh] Termos MeSH secundário: Formação de Anticorpos
Linfócitos B/imunologia
Proteína DEAD-box 58/genética
Proteína DEAD-box 58/imunologia
Células Dendríticas/imunologia
Dengue/genética
Dengue/virologia
Seres Humanos
Helicase IFIH1 Induzida por Interferon/genética
Helicase IFIH1 Induzida por Interferon/imunologia
Interleucina-27/genética
Interleucina-27/imunologia
Interleucinas/genética
Interleucinas/imunologia
Ativação Linfocitária
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Viral); 0 (Interleukin-27); 0 (Interleukins); 0 (interleukin-21); EC 3.6.1.- (DDX58 protein, human); EC 3.6.1.- (IFIH1 protein, human); EC 3.6.4.13 (DEAD Box Protein 58); EC 3.6.4.13 (Interferon-Induced Helicase, IFIH1)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180109
[Lr] Data última revisão:
180109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171130
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006738


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[PMID]:28468877
[Au] Autor:Buranapraditkun S; Pissani F; Teigler JE; Schultz BT; Alter G; Marovich M; Robb ML; Eller MA; Martin J; Deeks S; Michael NL; Streeck H
[Ad] Endereço:U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
[Ti] Título:Preservation of Peripheral T Follicular Helper Cell Function in HIV Controllers.
[So] Source:J Virol;91(14), 2017 Jul 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The maturation process of high-affinity antibodies is a result of intricate interactions between B cells and follicular helper T (Tfh) cells occurring in lymphoid germinal centers. HIV infection induces significant chronic immune activation, phenotypic skewing, and inflammation driven by years of continuous viral replication. High levels of viremia as well as immune activation and dysfunction have been demonstrated to have a perturbing impact on the B cell memory compartment and contribute to B cell exhaustion. Counterintuitively, the factors associated with perturbation of the B cell compartment seem to be favorable for the generation of highly affinity-matured Env-specific antibodies in a minority of HIV-infected individuals. Thus, the impact of HIV antigenemia on B cells and Tfh cell interactions warrants further exploration. We therefore studied immunophenotypes of HIV-specific B cells in individuals with differing levels of viral control using HIV Env gp120 probes and characterized the functionality of matched T cells in peripheral blood. While CXCR5 CD4 T cells were significantly diminished in HIV progressors, we found that a small subset of gp120-specific interleukin-21 (IL-21)-secreting CXCR5 CD4 T cells were significantly associated with gp120-specific B cell frequencies. In contrast, neither bulk CXCR5 CD4 T cells nor other HIV antigen specificities were associated with gp120-specific B cell levels. HIV-specific B cells derived from elite controllers displayed greater amounts of gp120-specific B cells in the resting memory subset, whereas HIV-specific B cells in progressors accumulated in tissue-like and activated memory subsets. Furthermore, CXCR5 CD4 T cells from elite controllers showed a stronger capacity to induce B cell maturation and immunoglobulin class switching than cells from HIV progressors. Dissecting the factors that are involved in B cell maturation and antibody development is important for HIV vaccine design. In this study, we found that HIV Env-specific CXCR5 CD4 T cells that secrete interleukin-21 are strongly associated with B cell memory phenotypes and function. Moreover, we found that the immune responses of HIV controllers showed intrinsically better helper activity than those of HIV progressors.
[Mh] Termos MeSH primário: Linfócitos B/imunologia
Centro Germinativo/imunologia
Proteína gp120 do Envelope de HIV/imunologia
Infecções por HIV/imunologia
Sobreviventes de Longo Prazo ao HIV
Linfócitos T Auxiliares-Indutores/imunologia
[Mh] Termos MeSH secundário: Adulto
Linfócitos T CD4-Positivos/química
Linfócitos T CD4-Positivos/imunologia
Feminino
Seres Humanos
Imunofenotipagem
Interleucinas/secreção
Masculino
Meia-Idade
Receptores CXCR5/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CXCR5 protein, human); 0 (HIV Envelope Protein gp120); 0 (Interleukins); 0 (Receptors, CXCR5); 0 (interleukin-21)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171226
[Lr] Data última revisão:
171226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE



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