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Protection conferred by heterologous vaccination against tuberculosis is dependent on the ratio of CD4(+)/CD4(+) Foxp3(+) cells

Fedatto, Paola Fernanda; Sergio, Cassia Alves; Oliveira e Paula, Marina; Gembre, Ana Flavia; Franco, Luis Henrique; Wowk, Pryscilla Fanini; Ramos, Simone Gusmao; Horn, Cynthia; Marchal, Gilles; Turato, Walter Miguel; Silva, Celio Lopes; da Fonseca, Denise
Fonte: WILEY-BLACKWELL; HOBOKEN Publicador: WILEY-BLACKWELL; HOBOKEN
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
36.6%
CD4(+) Foxp3(+) regulatory T cells inhibit the production of interferon-?, which is the major mediator of protection against Mycobacterium tuberculosis infection. In this study, we evaluated whether the protection conferred by three different vaccines against tuberculosis was associated with the number of spleen and lung regulatory T cells. We observed that after homologous immunization with the 65 000 molecular weight heat-shock protein (hsp 65) DNA vaccine, there was a significantly higher number of spleen CD4(+) Foxp3(+) cells compared with non-immunized mice. Heterologous immunization using bacillus Calmette Guerin (BCG) to prime and DNA-hsp 65 to boost (BCG/DNA-hsp 65) or BCG to prime and culture filtrate proteins (CFP)-CpG to boost (BCG/CFP-CpG) induced a significantly higher ratio of spleen CD4(+)/CD4(+) Foxp3(+) cells compared with non-immunized mice. In addition, the protection conferred by either the BCG/DNA-hsp 65 or the BCG/CFP-CpG vaccines was significant compared with the DNA-hsp 65 vaccine. Despite the higher ratio of spleen CD4(+)/CD4(+) Foxp3(+) cells found in BCG/DNA-hsp 65-immunized or BCG/CFP-CpG-immunized mice, the lungs of both groups of mice were better preserved than those of DNA-hsp 65-immunized mice. These results confirm the protective efficacy of BCG/DNA-hsp 65 and BCG/CFP-CpG heterologous prime-boost vaccines and the DNA-hsp 65 homologous vaccine. Additionally...

Identificação de epitopos da protease de HIV-1 alvos de respostas de células T CD4+ em pacientes infectados pelo HIV-1; Identification of HIV-1 protease epitopes target of CD4+ T cell responses in HIV-1 infected patients

Muller, Natalie Guida
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 18/12/2009 PT
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36.66%
Introdução: Uma proporção significante de pacientes infectados por HIV-1 (pacientes HIV-1+) tratados com inibidores de protease (IPs) desenvolve mutações de resistência. Estudos recentes têm mostrado que células T CD8+ de pacientes HIV- 1+ reconhecem epitopos de Pol incluindo mutações selecionadas por drogas. Nenhum epitopo CD4+ da protease foi descrito na base de dados de Los Alamos. Objetivo: Considerando que a protease de HIV-1 é alvo de terapia antiretroviral e que essa pressão pode selecionar mutações, nós investigamos se mutações selecionadas por IPs afetariam o reconhecimento de epitopos da protease de HIV-1 por células T CD4+ em pacientes tratados com IPs. Nós investigamos o reconhecimento de três regiões da protease preditas de conter epitopos de células T CD4+ bem como mutações induzidas por IPs por células T CD4+ em pacientes HIV- 1+ tratados com IPs. Materiais e Métodos: Quarenta pacientes HIV-1+ tratados com IPs foram incluídos (30 em uso de Lopinavir/ritonavir, 9 em uso de Atazanavir/Ritonavir e 1 em uso exclusivo de Atazanavir). Para cada paciente determinou-se a seqüência endógena da protease de HIV-1, genotipagem viral e tipagem HLA classe II. Utilizamos o algoritmo TEPITOPE para selecionar peptídeos promíscuos...

Análise da imunogenicidade de uma vacina de DNA codificando epitopos CD4 promíscuos e conservados do HIV-1 em camundongos BALB/c e transgênicos para moléculas de HLA classe II; Immunogenicity analysis of a DNA vaccine encoding promiscuous and conserved HIV-1 CD4 epitopes in BALB/c and HLA class II transgenic mice

Ribeiro, Susan Pereira
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 26/08/2010 PT
Relevância na Pesquisa
36.64%
Abordagens atuais no desenho de vacinas contra o HIV-1 estão focadas em imunógenos que codificam proteínas inteiras do HIV-1 e visam induzir respostas citotóxicas específicas. É concebível que vacinas bem-sucedidas devem induzir respostas contra múltiplos epitopos do HIV-1, coincidindo com seqüências das cepas circulantes do vírus, conhecido por sua grande variabilidade genética. Sabe-se que células T CD4+ são necessárias para indução de respostas efetivas de linfócitos T CD8+ citotóxicos. Neste trabalho, nós avaliamos a imunogenicidade de uma vacina de DNA codificando 18 epitopos para linfócitos T CD4+, conservados e ligadores de múltiplas moléculas HLA-DR em camundongos BALB/c e em quatro linhagens de camundongos transgênicos para moléculas de HLA classe II. Os camundongos imunizados apresentaram respostas de amplitude e magnitude significativas com proliferação e secreção de citocinas por linfócitos T CD4+ e T CD8+. Onze dos 18 epitopos para linfócitos T CD4+ presentes na vacina foram reconhecidos pelas linhagens de camundongos transgênicos para moléculas de HLA classe II. Em suma, 17 dos 18 epitopos codificados pela vacina foram reconhecidos. As células induzidas pela vacina apresentaram um perfil polifuncional com tipo 1 de citocinas...

Reprogramming the immune system with anti-CD4 monoclonal antibodies

Duarte, Joana Duarte Nunes, 1981-
Fonte: Universidade de Lisboa Publicador: Universidade de Lisboa
Tipo: Tese de Doutorado
Publicado em //2010 ENG
Relevância na Pesquisa
36.7%
Tese de doutoramento, Ciências Biomédicas (Imunologia), Universidade de Lisboa, Faculdade de Medicina, 2011; Immune tolerance is a state where the immune system does not respond aggressively towards a set of antigens while remaining fully competent to mount protective responses. The immune system is usually tolerant to our own antigens (self), to food antigens (oral tolerance), and to several other foreign substances to which we are regularly exposed (such as pollens and other potential allergens). Nevertheless, under certain conditions (genetic or environmental) there is a breakdown of tolerance to certain antigens, thus originating the onset of autoimmune and allergic pathologies. Regulatory T cells (Tregs) are central players in the maintenance of peripheral tolerance, having an essential role in preventing autoimmunity, as well as hypersensitivity reactions. However, the molecular mechanisms which mediate suppression are still obscure, and their investigation is a current priority, as it may reveal important targets for immune intervention. Studies in mouse models show that monoclonal antibodies (mAbs) targeting key lymphocyte molecules are able to produce long‐term tolerance following a shortterm therapy. This concept became known as immune reprogramming or therapeutic tolerance induction. Non‐depleting anti‐CD4 mAb have been shown to induce long term tolerance in transplantation through induction of Treg cells. Here I describe my research on the impact of non‐depleting anti‐CD4 mAb in different immune‐mediated pathologies aiming to reprogram the immune system towards tolerance induction. Furthermore...

The role of IL-7 in the homeostasis of human naive and memory CD4+T cell subsets

Azevedo, Rita Isabel Silva de, 1982-
Fonte: Universidade de Lisboa Publicador: Universidade de Lisboa
Tipo: Tese de Doutorado
Publicado em //2010 ENG
Relevância na Pesquisa
36.68%
Tese de doutoramento, Ciências Biomédicas (Imunologia), Universidade de Lisboa, Faculdade de Medicina, 2011; The main focus of this work is to study the homeostasis of human naive and memory CD4+ T cell subsets, particularly assessing the role of IL-7 in this process. For this purpose, we assessed the potentially distinct effects of IL-7 in the homeostasis of naive CD4+ T cell subsets defined by CD31 expression. We describe for the first time the preferential proliferation of the CD31+ subset within adult naive CD4+ T cells in response to IL-7 stimulation. Furthermore, we showed that IL-7-induced proliferation sustained or even increased the level of CD31 expression in CD31+ naive CD4+ T cells, although it did not induce CD31 re-expression in the CD31- subset. We also demonstrated that both IL-7- induced proliferation and CD31 maintenance were dependent on the PI3K pathway. Furthermore, we investigated the mechanisms involved in the restoration of T cell homeostasis following haploidentical haematopoietic stem cell transplantation (HSCT), particularly in the maintenance of the CD31+ naive CD4+ T cell pool. Our data suggest that long term immune reconstitution was successfully achieved in a cohort of haploidentical HSCT recipients...

Contribution of CD4+ T cells to the early mechanisms of ischemia- reperfusion injury in a mouse model of acute renal failure

Pinheiro,H.S.; Camara,N.O.S.; Noronha,I.L.; Maugeri,I.L.; Franco,M.F.; Medina,J.O.A.P.; Pacheco-Silva,A.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/04/2007 EN
Relevância na Pesquisa
36.6%
Renal ischemia-reperfusion (IR) injury is the major cause of acute renal failure in native and transplanted kidneys. Mononuclear leukocytes have been reported in renal tissue as part of the innate and adaptive responses triggered by IR. We investigated the participation of CD4+ T lymphocytes in the pathogenesis of renal IR injury. Male mice (C57BL/6, 8 to 12 weeks old) were submitted to 45 min of ischemia by renal pedicle clamping followed by reperfusion. We evaluated the role of CD4+ T cells using a monoclonal depleting antibody against CD4 (GK1.5, 50 µ, ip), and class II-major histocompatibility complex molecule knockout mice. Both CD4-depleted groups showed a marked improvement in renal function compared to the ischemic group, despite the fact that GK1.5 mAb treatment promoted a profound CD4 depletion (to less than 5% compared to normal controls) only within the first 24 h after IR. CD4-depleted groups presented a significant improvement in 5-day survival (84 vs 80 vs 39%; antibody treated, knockout mice and non-depleted groups, respectively) and also a significant reduction in the tubular necrosis area with an early tubular regeneration pattern. The peak of CD4-positive cell infiltration occurred on day 2, coinciding with the high expression of ßC mRNA and increased urea levels. CD4 depletion did not alter the CD11b infiltrate or the IFN-g and granzyme-B mRNA expression in renal tissue. These data indicate that a CD4+ subset of T lymphocytes may be implicated as key mediators of very early inflammatory responses after renal IR injury and that targeting CD4+ T lymphocytes may yield novel therapies.

Evaluating total lymphocyte counts as a substitute for CD4 counts in the follow up of AIDS patients

Angelo,Ana Luiza Dias; Angelo,Camila Dias; Torres,Alex José Leite; Ramos,André Maurício Costa; Lima,Márcia; Netto,Eduardo Martins; Brites,Carlos
Fonte: Brazilian Society of Infectious Diseases Publicador: Brazilian Society of Infectious Diseases
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/10/2007 EN
Relevância na Pesquisa
36.61%
This study evaluated total lymphocyte count (TLC) as a substitute marker for CD4+ cell counts to identify patients who need prophylaxis against opportunistic infection (CD4 < 200 cells/mm³) and patients with CD4 < 350 cells/mm³ (Brazilian threshold value of CD4 count to define AIDS). We evaluated TLC and CD4+ cells count of 1,174 HIV-infected patients, in Salvador, Brazil, from May 2003 to September 2004. CD4+ cell counts were performed by flow cytometry, and TLC was measured with an automated hematological counter. The mean CD4 count was 430 cells/mm³ (range: 4 to 2,531 cells/mm³). Mean TLC was 1,900 cells/mm³ (range: 300 to 6,200 cells/mm³). Using a threshold value of 1,000 cells/mm³ for TLC, the positive predictive value (PPV) was 77% for CD4 < 200 cells/mm³, but the sensitivity was only 29%, while the negative predictive value (NPV) was 88%, with 98% specificity. Similar findings were observed for CD4 count < 350. Using the same threshold value of 1,000 cells/mm³ for TLC, sensitivity was 14%, and specificity 99% (PPV= 94%; NPV=62%). In 70/1,510 (5%) of the samples the sum of CD4 and CD8 cell counts was greater than the TLC and in 27% (419/1,510) this sum was below 65% of the TLC. TLC has a high specificity to identify patients for prophylaxis...

SIV envelope glycoprotein determinants of macrophage tropism and their relationship to neutralization sensitivity and CD4-independent cell-to-cell transmission

Yen, Po-Jen
Fonte: Harvard University Publicador: Harvard University
Tipo: Thesis or Dissertation
EN_US
Relevância na Pesquisa
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Macrophages are target cells for human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection that serve as viral reservoirs in brain, lung, gut, and other tissues, and play important roles in disease pathogenesis, particularly HIV/SIV-associated neurological disease. Macrophages express low levels of the HIV/SIV receptor CD4, but mechanisms by which macrophage-tropic viruses use low CD4 to mediate spreading infections are poorly understood. One mechanism involves enhanced envelope glycoprotein (Env) interaction with CD4 or CCR5, but this phenotype is frequently associated with increased neutralization sensitivity to antibodies targeting CD4/CCR5 binding sites. Moreover, this mechanism does not explain how these neutralization-sensitive viruses evade immune responses while establishing spreading infections. In this dissertation, we sought to identify SIV Env determinants for macrophage tropism and characterize mechanisms by which they enhance virus replication in macrophages. To identify viral variants capable of inducing macrophage-associated pathogenesis, we cloned Env sequences from SIV-infected macaques at early and late stage infection, and identified an early variant in blood that shares >98% sequence identity with the consensus sequence of late variants in brain from macaques with neurological disease. SIV clones encoding this Env variant mediated high levels of fusion...

CD4 Recovery on Antiretroviral Therapy Is Associated With Decreased Progression to Liver Disease Among Hepatitis C Virus-Infected Injecting Drug Users

Anderson, Jeffrey P.; Horsburgh, C. Robert; Williams, Paige L.; Tchetgen Tchetgen, Eric J.; Nunes, David; Cotton, Deborah; Seage, George R.
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
EN_US
Relevância na Pesquisa
36.61%
Background. Human immunodeficiency virus (HIV) coinfection accelerates liver disease progression in individuals with chronic hepatitis C. We evaluated the associations of CD4, HIV RNA, and antiretroviral therapy (ART)-induced CD4 recovery with liver diagnoses in a prospective cohort of injecting drug users (IDUs). Methods. We evaluated 383 coinfected IDUs in the Boston area, prospectively observed for a median of 1.8 years. Liver disease progression included the first occurrence of hepatocellular carcinoma, variceal bleeding, ascites, encephalopathy, or death due to hepatic failure. Multivariable-adjusted extended Cox models were specified to estimate hazard ratios (HRs) for comparisons of CD4, change in CD4 (from nadir), and HIV RNA with respect to liver disease progression events. Results. Twenty-four persons experienced a liver disease progression event over 1155 person-years (2.1 per 100 person-years), including 20 deaths attributed to end-stage liver disease (1.7 per 100 person-years). CD4 at baseline and over follow-up strongly predicted liver disease progression (baseline CD4 <200 vs ≥200: HR = 5.23, 95% confidence interval [CI], 2.30–11.92; time-updated CD4 <200 vs ≥200: HR = 11.79, 95% CI, 4.47–31.07). Nadir CD4 was also a strong indicator (<100 vs ≥100: HR = 3.52...

The Influence of Innate Immune Mechanisms on CD4+ and CD8+ T Cell Responses

Llamas, Fernando Ontiveros ; Livingstone, Alexandra M.
Fonte: Universidade de Rochester Publicador: Universidade de Rochester
Tipo: Tese de Doutorado
ENG
Relevância na Pesquisa
36.63%
Thesis (Ph.D.)--University of Rochester. School of Medicine and Dentistry. Dept. of Microbiology and Immunology, 2007.; CD4+ T cells play multiple roles within the adaptive immune system. One of these roles concerns the qualitative and quantitative modification of the CD8+ T cell response, a phenomenon termed CD4 help. Although primary CD8 responses against pathogens are largely independent of the presence of CD4+ T cells, responses directed to cell-associated antigens show variable dependence on CD4 help. This variability is likely a result of the different degrees of activation of the innate immune system inherent in diverse models of immunization. Our laboratory has developed a Dendritic Cell-based model of immunization that shows a strong dependency on CD4 help. We used this model and a traditional crosspriming system to test the hypothesis that in pathogen-free systems, either inflammation or activation of NK cells would be instrumental in the generation of primary CD8 responses in the absence of CD4 help. Such immune responses could prove detrimental if resulting in unchecked expansion of self-reactive CD8 T cells or beneficial in immunocompromised individuals with deficient CD8 responses due to the lack of a functional CD4+ compartment. We found that neither NK cell activation nor exposure to the inflammatory cytokine TNF! was sufficient to bypass the requirement for CD4 help. However...

Role of CD4+ T cells in the regulation of the immune response against encapsulated Group B Streptococcus

Clarke, Damian
Fonte: Université de Montréal Publicador: Université de Montréal
Tipo: Thèse ou Mémoire numérique / Electronic Thesis or Dissertation
EN
Relevância na Pesquisa
36.63%
Le Streptocoque de groupe B (GBS) est un important agent d’infection invasive pouvant mener à la mort et demeure la cause principale de septicémie néonatale à ce jour. Neuf sérotypes ont été officiellement décrits basés sur la composition de la capsule polysaccharidique (CPS). Parmi ces sérotypes, le type III est considéré le plus virulent et fréquemment associé aux maladies invasives graves, telle que la méningite. Malgré que plusieurs recherches aient été effectuées au niveau des interactions entre GBS type III et les cellules du système immunitaire innées, aucune information n’est disponible sur la régulation de la réponse immunitaire adaptative dirigée contre ce dernier. Notamment, le rôle de cellules T CD4+ dans l’immuno-pathogenèse de l’infection causée par GBS n’a jamais été étudié. Dans cet étude, trois différents modèles murins d’infection ont été développé pour évaluer l’activation et la modulation des cellules T CD4+ répondantes au GBS de type III : ex vivo, in vivo, et in vitro. Les résultats d’infections ex vivo démontrent que les splénocytes totaux répondent à l’infection en produisant des cytokines de type-1 pro-inflammatoires. Une forte production d’IL-10 accompagne cette cascade inflammatoire...

Einfluss von Hsp70 auf die Proliferation antigenspezifischer humaner CD4+ T-Zellen nach Peptidstimulation; Effect of Hsp70 on the proliferation of antigen specific human CD4+ T-cells after stimulation with antigenic peptides

Lühl, Simon Felix
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
DE_DE
Relevância na Pesquisa
36.6%
In der vorliegenden Arbeit wurde der Hsp70-Einfluss auf die Immunantwort im humanen System im Zusammenhang mit autoantigenen Peptiden untersucht. Mittels HLA-DR Tetrameren wurde in vitro die spezifische CD4+ T-Zellantwort gesunder HLA-typisierter Spender auf autoantigene Peptide charakterisiert. Die Kernfragen waren, welchen Einfluss Tregs auf die Expansion antigenspezifischer T-Zellen haben, ob durch Hsp70-gebundenes Peptid autoantigenspezifische CD4+ T-Zellen verstärkt aktiviert werden und wie Hsp70 die Zytokinproduktion der T-Zellen verändert. Es wurde gezeigt, dass die Depletion der Tregs nicht in jedem Fall notwendig ist, um eine Proliferation der autoreaktiven T-Zellen auszulösen. Hsp70 scheint in Komplexierung mit autoantigenen Peptiden bei der Stimulation von CD4+ T-Zellen einen Einfluss zu haben, allerdings statistisch nicht signifikant. In einem durchflusszytometrischen Zytokinassay wurde, bei Stimulation mit Peptid:Hsp70-Komplex eine gegenüber Stimulation mit Peptid alleine, verringerte Produktion des pro-inflammatorischen TH1-Zytokins IFN-gamma im Sinne einer TH2-Antwort gezeigt. Dies wurde im Zytokin-ELISA mit einer zweiten Methode und zusätzlich anhand von IL-5 bestätigt. Für das TH2-Zyotokin IL-5 wurde bei einem tumorassoziierten Antigen eine statistisch signifikant vermehrte Produktion gemessen. Insgesamt wurde kein eindeutiger Hsp70-Effekt auf die autoantigenspezifische CD4+ T-Zellaktivierung gezeigt...

Étude du mécanisme par lequel la thérapie à l'IL7 induit l'expansion homéostatique des lymphocytes T CD4+

Hennion-Tscheltzoff, Olga
Fonte: Université de Montréal Publicador: Université de Montréal
Tipo: Thèse ou Mémoire numérique / Electronic Thesis or Dissertation
FR
Relevância na Pesquisa
36.68%
Dans les cas de lymphopénie, les lymphocytes T résiduels prolifèrent exagérément dans un phénomène appelé «expansion homéostatique périphérique» (HPE), qui est efficace pour la régénération des T CD8+, mais inefficace pour les T CD4+. L’interleukine-7 (IL7) est une cytokine homéostatique utilisée afin d’augmenter les comptes lymphocytaires T des patients lymphopéniques. Toutefois, la raison de l’expansion préférentielle des lymphocytes T CD8+ par l’IL7 demeure toujours inconnue. Nous montrons que cette expansion est due au fait que l’IL7 induit une prolifération efficace des T CD8+ périphériques (CD8+PERI) ainsi que des émigrants thymiques CD8+ (CD8+RTEs). Par contre, l’effet prolifératif de l’IL7 est restreint presqu’uniquement aux CD4+RTEs même si les CD4+PERI survivent mieux que les CD4+RTEs. De plus faibles doses d’IL7 sont nécessaires aux CD4+RTEs afin de phosphoryler STAT5 ou de proliférer comparativement aux CD4+PERI et nous démontrons que les contacts TCR/CMHII sont nécessaires à la prolifération induite par l’IL7 des CD4+RTEs en périphérie. De fait, augmenter au Flt3 ligand le nombre de cellules dendritiques périphériques d’une souris donneuse, avant de transférer ses TPERI dans des souris receveuses traitées à l’IL7 induit une prolifération significative des CD4+PERI. Nos résultats indiquent donc que l’abondance des contacts TCR/CMHII reçus dans le thymus semble contrôler la sensibilité à l’IL7 des CD4+RTEs. Finalement...

Analyse du mécanisme de la dégradation du récepteur CD4 par la protéine Vpu du virus de l'immunodéficience humaine-1 (VIH-1)

Binette, Julie
Fonte: Université de Montréal Publicador: Université de Montréal
Tipo: Thèse ou Mémoire numérique / Electronic Thesis or Dissertation
FR
Relevância na Pesquisa
36.72%
Le VIH-1 a développé plusieurs mécanismes menant à la dégradation de son récepteur cellulaire, la molécule CD4, dans le but d’augmenter la relâche de particules virales infectieuses et d’éviter que la cellule soit surinfectée. L’un de ces mécanismes est la dégradation, induite par la protéine virale Vpu, du CD4 nouvellement synthétisé au niveau du réticulum endoplasmique (RE). Vpu doit lier CD4 et recruter l’ubiquitine ligase cellulaire SCFβ-TrCP, via sa liaison à β-TrCP, afin de dégrader CD4. Puisque CD4 doit être retenu au RE pour permettre à Vpu d’induire sa dégradation via le système ubiquitine-protéasome, il a été suggéré que ce processus implique un mécanisme semblable à une voie cellulaire de dégradation des protéines mal-repliées appelée ERAD (« endoplasmic reticulum-associated degradation »). La dégradation par ERAD implique généralement la dislocation des protéines du RE vers le cytoplasme afin de permettre leur poly-ubiquitination et leur dégradation par le protéasome. Nous avons démontré que Vpu induit la poly-ubiquitination de CD4 dans des cellules humaines. Nos résultats suggèrent aussi que CD4 doit subir une dislocation afin d’être dégradé par le protéasome en présence de Vpu. De plus...

Perfil de expressão de genes da via Wnt/beta-catenina em timócitos e linfócitos T CD4+ de camundongos BALB/c; Gene expression profile of Wnt/beta-catenin pathway elements in thymocytes and CD4 + T lymphocytes of BALB/c mice.

Ali, Taccyanna Mikulski
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 27/08/2015 PT
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INTRODUÇÃO: A molécula HIG2 pode atuar como agonista da via Wnt/beta-catenina, pois se liga ao receptor Frizzled 10 e induz a expressão de genes da mesma. Dados recentes do nosso grupo mostraram expressão diferencial do gene HIG2 em células mononucleares do sangue periférico e em especial linfócitos T CD4+ naïve, mas não em células diferenciadas de memória em indivíduos sadios. Também observamos in vitro em linfócitos T CD4+ de indivíduos saudáveis que o peptídeo sintético HIG2 induziu a ativação da via Wnt/beta-catenina, produção de HIG2 e outros produtos da via, além da proliferação de células T CD4+ naïve sugerindo um papel do HIG2 na proliferação homeostática de linfócitos T CD4+. HIPÓTESE: Como as células T CD4+ naïve são diretamente exportadas pelo timo, os níveis aumentados de HIG2 neste tipo celular sejam decorrentes da ativação da via Wnt/?-catenina nos estágios tardios da diferenciação de timócitos. Portanto, as células T CD4+ naïve e timócitos simples positivos para CD4 (SP CD4) apresentariam perfil semelhante de expressão de HIG2 e genes da via Wnt/beta-catenina, incluindo receptores, fatores de transcrição, genes estruturais da via e alvos quando comparadas as demais populações celulares. OBJETIVO: Avaliar a expressão de HIG2 e outros genes da via Wnt/beta-catenina em timócitos e linfócitos T CD4+ naïve e memória de camundongos. MÉTODOS: Isolamos timócitos duplo negativos (DN)...

Blocking of HIV-1 infection by targeting CD4 to nonraft membrane domains

Real, Gustavo del; Jiménez Baranda, Sonia; Lacalle, Rosa Ana; Mira, Emilia; Lucas, Pilar; Gómez Moutón, Concepción; Carrera, Ana C.; Martínez-Alonso, Carlos; Mañes, Santos
Fonte: Rockefeller University Press Publicador: Rockefeller University Press
Tipo: Artículo Formato: 374917 bytes; application/pdf
ENG
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36.6%
Copyright © by The Rockefeller University Press; Human immunodeficiency virus (HIV)-1 infection depends on multiple lateral interactions between the viral envelope and host cell receptors. Previous studies have suggested that these interactions are possible because HIV-1 receptors CD4, CXCR4, and CCR5 partition in cholesterol- enriched membrane raft domains. We generated CD4 partitioning mutants by substituting or deleting CD4 transmembrane and cytoplasmic domains and the CD4 ectodomain was unaltered. We report that all CD4 mutants that retain raft partitioning mediate HIV-1 entry and CD4-induced Lck activation independently of their transmembrane and cytoplasmic domains. Conversely, CD4 ectodomain targeting to a nonraft membrane fraction results in a CD4 receptor with severely diminished capacity to mediate Lck activation or HIV-1 entry, although this mutant binds gp120 as well as CD4wt. In addition, the nonraft CD4 mutant inhibits HIV-1 X4 and R5 entry in a CD4 cell line. These results not only indicate that HIV-1 exploits host membrane raft domains as cell entry sites, but also suggest new strategies for preventing HIV-1 infection.; Peer reviewed

The mechanism of HIV-1 Nef-mediated downregulation of CD4

Chaudhuri, Rittik
Fonte: University of Cambridge; Department of Clinical Biochemistry; National Institutes of Health; Magdalene College Publicador: University of Cambridge; Department of Clinical Biochemistry; National Institutes of Health; Magdalene College
Tipo: Thesis; doctoral; PhD
EN
Relevância na Pesquisa
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Nef, an accessory protein of HIV-1, is a critical determinant of viral pathogenicity. The pathogenic effects of Nef are in large part dependent on its ability to decrease the amount of CD4 on the surface of infected cells. Early studies suggested that Nef induces downregulation by linking the cytosolic tail of CD4 to components of the host-cell protein-trafficking machinery. However, the specific sorting pathway that Nef uses to modulate CD4 expression remained uncertain. According to one model, Nef was thought to interfere with the transport of newly synthesized CD4 from the TGN to the cell-surface. Another model claimed that Nef facilitated the removal of CD4 from the plasma membrane. The primary goal of this thesis was to determine which of these models was correct. To accomplish this objective, a novel Nef-CD4 system was developed in Drosophila S2 cells. Nef was not only able to downregulate human CD4 in S2 cells, but it did so in a manner that was phenotypically indistinguishable from its activity in human cells. An RNAi screen targeting protein-trafficking genes in S2 cells revealed a requirement for clathrin and the clathrin-associated, plasma membrane-localized AP-2 complex in the Nef-mediated downregulation of CD4. In contrast...

Aumento de células T CD4+CD69+ e redução de células T reguladoras CD4+CD25+FoxP3+ em camundongos com Lúpus Eritematoso Sistêmico (LES) induzido por pristane; Increase of CD4+CD69+ T cells and reduction of CD4+CD25+FoxP3+ regulatory T cells in pristane-induced mice with systemic lupus erythematosus (SLE)

Peixoto, Tatiana Vasconcelos
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 25/09/2015 PT
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Introdução: O Lúpus Eritematoso Sistêmico (LES) é uma doença autoimune multissistêmica de etiologia complexa que envolve fatores ambientais, genéticos e hormonais. É caracterizada pela produção de autoanticorpos e mediadores inflamatórios, ativação e proliferação de células T autorreativas e perda da autotolerância imunológica. Em pacientes com LES, a expressão do receptor primário de ativação CD69 é aumentada e a de células T supressoras/reguladoras (Treg) CD4+CD25+FoxP3+ é reduzida. O CD69 é essencial para ativação de células T CD4 autorreativas enquanto que as células Treg são importantes na manutenção da autotolerância. Desta forma, células T tem um papel central na patogênese do LES, mas os mecanismos implicados na falência da autotolerância ainda não são elucidados, destacando a importância de estudos em modelos experimentais da doença, como o de LES-induzido por pristane. Objetivo: Quantificar células T CD4+CD69+ ativadas e Treg CD4+CD25+FoxP3+ no sangue, baço e LP de camundongos Balb/c LESinduzido por pristane no sentido de avaliar a falência de autotolerância neste modelo. Métodos: Analisamos 84 camundongos Balb/c fêmeas: 52 receberam por via intraperitoneal uma dose única de 0...

A quantificação de CD4+ e CD8+ portal em hepatite C crônica está relacionada com a intensidade da hepatite de interface; Portal cd4+ and cd8+ t lymphocyte correlate to intensity of interface hepatitis in chronic hepatitis C

Viso, Ana Teresa Rodriguez; Barbosa, Thaís de Castro; Yamamoto, Lídia; Pagliari, Carla; Fernandes, Elaine Raniero; Brasil, Roosecelis Araújo; Andrade Junior, Heitor Franco de; Duarte, Maria Irma Seixas; Barone, Antônio Alci
Fonte: Universidade de São Paulo. Instituto de Medicina Tropical de São Paulo Publicador: Universidade de São Paulo. Instituto de Medicina Tropical de São Paulo
Tipo: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion; ; ; ; ; Formato: application/pdf
Publicado em 01/12/2007 ENG
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INTRODUÇÃO: A patogênese da hepatite C crônica ainda está em discussão. Sabe-se que linfócitos T (LT) CD4+ e CD8+ são tipicamente observados no espaço portal e peri-portal de pacientes com hepatite C crônica, mas o conhecimento exato de suas ações no fígado, bem como sua influência na progressão da doença hepática ainda estão em discussão. MÉTODOS: Os LT CD4+ e T CD8+ foram quantificados por imunohistoquímica nos espaços porta e peri-portais em 39 biópsias hepáticas de pacientes cronicamente infectados pelo vírus da hepatite C. Esses dados foram associados com os dados demográficos, as alterações histológicas, os achados laboratoriais dos pacientes com hepatite C e com os genótipos do vírus da hepatite C. RESULTADOS: Houve grande quantidade tanto de LT CD4+ como de CD8+, sendo que houve maior densidade de LTCD4+ do que CD8+ nos espaços portal e peri-portal. Tanto o número de linfócitos T CD4+ como de CD8+ foram diretamente relacionados com a intensidade da hepatite de interface. Os linfócitos T CD8+ foram estatisticamente relacionados às enzimas hepáticas. CONCLUSÃO: O encontro de numerosos linfócitos T CD4+ e linfócitos T CD8+ no espaço-portal e peri-portal e sua correlação com a hepatite de interface sugerem que a evolução da hepatite C dependa da ação dos linfócitos T intra-hepáticos...

Estilo de vida de pacientes infectados pelo vírus da imunodeficiência humana (HIV) e sua associação com a contagem de linfócitos T CD4+; Lifestyle of HIV seropositives patients and your association with CD4 positive t-lymphocytes counts

de Lima Eidam, Cristiane; Mestre em Educação Física - UFSC; da Silva Lopes, Adair; Doutor do Departamento de Educação Física/UFSC, Florianópolis, SC, Brasil.; Crosland Guimarães, Mark Drew; Departamento de Medicina da Universidade Federal de Minas
Fonte: Universidade Federal de Santa Catarina. Florianópolis, SC. Brasil Publicador: Universidade Federal de Santa Catarina. Florianópolis, SC. Brasil
Tipo: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion; "Avaliado por Pares",; Avaliado por Pares; Descritiva Formato: application/pdf; application/pdf
Publicado em 19/11/2006 POR; ENG
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Este estudo pretendeu avaliar o estilo de vida de pacientes infectados pelo vírus da imunodeficiência humana (HIV) e associá-lo à contagem de linfócitos T CD4+. A amostra, selecionada por conveniência, foi constituída de 111 indivíduos (68 homens e 43 mulheres, com idade média de 37 anos). Os dados para avaliação do estilo de vida (hábitos alimentares, atividade física, comportamento preventivo, relacionamentos e controle do estresse), foram obtidos por meio de entrevista. Para a contagem do número de linfócitos T CD4+, considerou-se o resultado do último exame laboratorial apresentado na ficha do paciente. Foram realizadas análises descritivas, análise de variância (ANOVA) one-way, com o teste post hoc de Tukey e o teste qui–quadrado. Os resultados evidenciaram que a contagem média de linfócitos T CD4+ foi de 345 cel/mm3 e a mediana de 296 cel/mm3. A maioria dos pacientes realizava os exames de rotina e seguia as recomendações médicas (92,8%), usava preservativos durante as relações sexuais (80,2%), estava satisfeita com os relacionamentos (80,2%) e reservava tempo, todos os dias, para relaxar (82%). O perfil do estilo de vida, nos componentes hábitos alimentares e de atividade física habitual, foi classificado como insatisfatório. O comportamento preventivo foi a variável do estilo de vida com resultado médio significativamente superior aos demais (6...