Esporos de Bacillus subtilis apresentam propriedades adjuvantes, sendo capazes de aumentar a resposta humoral após a sua coadministração com antígenos misturados ou adsorvidos à sua superfície. Mas, para isso, é necessária a produção de esporos altamente purificados e com rendimentos elevados. Neste trabalho, realizamos com sucesso uma análise quantitativa das condições de esporulação e dos métodos de purificação, o que melhorou a reprodutibilidade do processo e a obtenção de amostras com elevado grau de pureza e rendimento. Avaliamos também as propriedades imunomodulatórias destes esporos, utilizando como antígeno modelo a proteína recombinante Gag-p24 do HIV-1. A coadministração, mas não a adsorção à superfície do esporo, aumentou a imunogenicidade do antígeno sem induzir efeitos deletérios após a administração parenteral em camundongos BALB/c e C57BL/6. Além de promoveram a ativação das APCs, os esporos interagem com receptores relacionados à imunidade inata, devido à ausência do efeito adjuvante em camundongos nocautes para TLR2. Esses resultados abrem perspectivas interessantes para a utilização de esporos como adjuvantes vacinais. / Bacillus subtilis spores have been shown to behave as vaccine adjuvants, promoting the increase of antibody responses after co-administration with antigens either admixed or adsorbed on the spore surface. Nonetheless, such specialized application requires highly purified spore preparations at high yields. In this work, we successfully performed a systematic quantitative analysis of sporulation conditions and spore purification methods, which improved the reproducibility of the process and the obtainment of samples with high purity and yield. Afterwards, we further evaluated the immune modulatory properties of these spores using a recombinant HIV-1 Gag-p24 protein as a model antigen. The co-administration, but not adsorption to the spore surface, enhanced the immunogenicity of that target antigen, without inducing deleterious effects, after subcutaneous administration to BALB/c and C57BL/6 mice. Besides promoting activation of antigen presenting cells, spores interact with receptors related to innate immunity, due to the absence of the adjuvant effect on TLR2 knockout mice. These results open interesting perspectives for the use of B. subtilis spores as vaccine adjuvants.

Submitted by Socorro Pontes (socorrop@ufersa.edu.br) on 2017-06-29T13:21:31Z No. of bitstreams: 1 RebecaJFC_DISSERT.pdf: 1231711 bytes, checksum: 845448c874cc7680ba5ba551b9029235 (MD5) / Made available in DSpace on 2017-06-29T13:21:31Z (GMT). No. of bitstreams: 1 RebecaJFC_DISSERT.pdf: 1231711 bytes, checksum: 845448c874cc7680ba5ba551b9029235 (MD5) Previous issue date: 2017-02-14 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Equine infectious anemia (EIA) is the most important viral disease among horses. It is an endemic disease in populations of Equidae throughout the world. All equids are considered to be susceptible although most of the published work are focused in horses, with a lack of information on EIA in donkeys. In the State of Rio Grande do Norte, Brazil thousands of donkeys live free, establishing a problem for the control of diseases like the EIA, since they may play a role as reservoirs. In this work, blood samples taken from 409 animals (asinine and equine) were submitted to IDGA, ELISA pgp45 and nested-PCR tests, using gag and LTR gene as molecular markers. Four samples (0.98%) were positive in at least one serological test, and of these, three (0.73%) were positive to nested-PCR. We did not get enough material for sequencing of LTR samples from asinine, then only the amplified referring to the positive equine sample was sequenced. The alignment (BLAST) allowed the identification of the sequence as EIAV with 95% of similarity with european strains. Three product from nested-PCR products for the gag gene were sequenced and submitted to phylogenetic analysis. The result of this analysis suggested that the samples obtained from the horse had the same origin as strains from North America, and that the sequences from donkey samples had no homology with any other already published available EIAV sequence. In the light of the results from this work, additional studies are required. So we could confirm that we found a new strain of EIAV or endogenous retrovirus that are capable of expressing genes that are homologous to EIAV or even a new species of lentivirus Although the presented data are incomplete, they reveal an interesting scenario for the study of EIAV infection in equids ther than the horses / A anemia infecciosa equina (AIE) é a doença infecciosa de etiologia viral mais importante entre os equinos. É uma doença endêmica em populações de equídeos por todo o mundo. Considera-se que todos os equídeos são susceptíveis embora os trabalhos publicados se concentrem em equinos, sendo escassas as informações sobre AIE em asininos. No Rio Grande do Norte (RN) milhares de asininos vivem livres, constituindo um problema para o controle de enfermidades como a AIE, pois podem ser prováveis reservatórios e fontes de transmissão delas. Neste trabalho, amostras de 409 animais (asininos e equinos) foram submetidas aos testes de IDGA, ELISA pgp45 e nested-PCR, utilizando iniciadores para o gene gag e LTR. Quatro amostras (0,98%) foram positivas em pelo menos um teste sorológico, e dessas, três amostras (0,73%) foram positivas na nested-PCR. Não obtivemos material suficiente para sequenciamento das amostras de LTR dos asininos sendo sequenciado apenas o amplificado de LTR referente à amostra do equino positivo. O alinhamento (BLAST) permitiu a identificação da sequência como vírus da AIE (EIAV) com 95% de similaridade de nucleotídeos com estirpes europeias. Os três produtos obtidos da nested-PCR para o gene gag foram sequenciados e submetidos à análise filogenética. O resultado da análise sugeriu que a sequência obtida do cavalo confirmaram a identificação como EIAV, com a mesma origem de isolados da América do Norte, e que as sequencias de asininos não possuem identidade com nenhuma outra deo EIAV até o momento publicada. Desta forma, estudos adicionais são necessários para confirmar se, com estes resultados, foram identificados um lentivirus ainda não descrito que infecta Equus asinus (e qual papel ele teria para outros equídeos) ou se trata de retrovírus endógenos que expressa proteínas usadas como marcadores de diagnóstico da AIE. Embora os dados apresentados sejam incipientes, revelam um cenário interessante para o estudo das lentiviroses em asininos / 2017-06-29

La protéine de nucléocapside (NC) du virus de l’immunodéficience humaine (VIH-1) joue de nombreux rôles dans les phases précoce et tardive de l’infection. La NC est une protéine à deux doigts de zinc, chaperonne des acides nucléiques. Nous avons cherché de nouveaux partenaires cellulaires de la NCp7 et identifié une protéine de liaison aux ARNs, Upstream of N-ras (Unr), dont l’interaction avec Gag et NCp7 a été confirmée. L’interaction entre Gag et Unr est dépendante de l’ARN et médiée par le domaine NC. Unr est une ITAF (IRES transacting factor) régulant la traduction médiée par plusieurs IRESs cellulaires et viraux. L’ARN génomique du VIH-1 possède deux IRESs dont un localisé dans la région non traduite en 5’ qui permet aux ARNm viraux de conserver un fort niveau de traduction lorsque la traduction coiffe-dépendante de la cellule est affaiblie par l’arrêt du cycle viral induit par l’infection. En utilisant un système de dual luciférase, nous avons montré qu’Unr est une ITAF dont la surexpression stimule l’IRES VIH-1. Des mutations ponctuelles de cet IRES, dans un motif consensus de liaison à Unr, altèrent à la fois l’activité de l’IRES et sa réponse à Unr suggérant que l’activité IRES dépend fortement de Unr. L’effet d’Unr sur l’IRES est inhibé par la surexpression de NCp7 mais pas par celle de Gag dont l’effet stimulateur sur l’IRES est additif de celui d’Unr suggérant un rôle d’Unr différent dans les phases précoce et tardive de l’infection. Pour finir, le knockdown de l’expression d’Unr entraîne une diminution significative de l’infection par un pseudovirus non réplicatif soulignant l’implication fonctionnelle d’Unr dans la phase précoce. / The Human Immunodeficiency Virus-1 (HIV-1) nucleocapsid protein (NC), as a mature protein (NCp7) or as a domain of the polyprotein Gag, plays several important roles in both the early and late phase of the infection. NC is a nucleic acid chaperone protein with two zinc fingers. We searched for new cellular protein partners of NCp7 and identified the RNA binding protein Unr, Upstream of N-ras, whose interaction with both Gag and NCp7 was confirmed. Unr interaction with Gag is RNA dependent and mediated by its NC domain. Unr is an ITAF (IRES trans-acting factor) regulating the translation driven by several IRESs. The HIV-1 genomic mRNA harbors two IRESs elements: one of them found within the HIV-1 5’-Untranslated region drives HIV-1 mRNA translation when the cap-dependent translation is diminished due to the infection-induced cell cycle arrest. Using a dual luciferase assay, Unr was shown to act as an ITAF, increasing the HIV-1 IRES dependent translation. Point mutations of the HIV-1 IRES in a consensus Unr binding motif were found to alter both the IRES activity and its activation by Unr suggesting a strong dependency of the IRES on Unr. Unr stimulation effect is furthermore counteracted by NCp7, but not by Gag overexpression, which increases the IRES activity in an additive manner to Unr suggesting a differential Unr effect on the early and late phases of the infection. Finally, knockdown of Unr in HeLa cells leads to a decline in infection by a non-replicative lentivector proving its functional implication in the early phase.

Innerhalb der Retroviren unterscheiden sich die Foamyviren (FV) bezüglich ihrer Proteinexpression, der Partikelmorphogenese und ihres Reproduktionszyklus deutlich von den Orthoretroviren. Im Rahmen dieser Arbeit wurden zwei exklusive Merkmale der Foamyviren, die ungewöhnliche Struktur des Gag-Proteins und die Gag unabhängige Pol-Expression, in ihrer Auswirkung auf Morphogenese und Zusammensetzung foamyviraler Partikel untersucht. Für die Morphogenese infektiöser Partikel sind sehr unterschiedliche Mengen der Genprodukte eines Retrovirus nötig. Im Gegensatz zu den Orthoretroviren wird bei Foamyviren das Produkt des pro/pol-ORFs von einer eigenen, gespleißten mRNA translatiert. Der Gag/Pro/Pol-Gehalt in den Viruspartikeln kann folglich nicht wie bei Orthoretroviren über eine gekoppelte Translation und Inkorporation von Gag- und Gag/Pro/Pol-Fusionsproteinen reguliert werden. In dieser Arbeit wurde der Frage nach dem molekularem Verhältnis von Gag- und Pro/Pol-Proteinen in foamyviralen Partikeln nachgegangen. In den isolierten PFV Partikeln war der relative Gehalt an dem Gag-Prozessierungsprodukt p68 viermal höher als der Gehalt an dem Gag-Vorläuferprotein p71. Das Gag-Prozessierungsprodukt p68 bildet somit das Hauptstrukturelement der PFV Kapside. Weiterhin ergab sich ein Verhältnis von 16 Gag-Molekülen zu einem p85PR/RT-Molekül sowie 10 Gag-Molekülen pro p40IN-Molekül. Damit entsprach die Gag/Pol-Zusammensetzung von PFV Partikeln den stöchiometrischen Verhältnissen in orthoretroviralen Partikeln von 10 - 20 Gag-Molekülen pro Pol-Molekül. Dieses Ergebnis ist in Hinsicht auf die unterschiedlichen Synthesestrategien von Gag und Pol bei Orthoretro- und Foamyviren bemerkenswert. Basierend auf diesen Ergebnissen stellt sich für weiterführende Untersuchungen nun die Frage nach der Regulation der Gag- und Pol-Synthese bei Foamyviren. Bei Orthoretroviren setzt sich in einem Prozess der Selbstorganisation das Strukturprotein Gag autonom zu virusähnlichen Partikeln zusammen, die auch in Abwesenheit weiterer viraler Komponenten aus der Wirtszelle freigesetzt werden. Foamyviren dagegen benötigen für die Freisetzung ihrer Viruspartikel neben dem Strukturprotein obligat die Koexpression ihres Glykoproteins. Im zweiten Teil dieser Arbeit wurden funktionelle Abschnitte im PFV Gag-Protein eingegrenzt und charakterisiert, die eine Rolle bei der Bildung und Freisetzung der viralen Partikel spielen. Eine schrittweise Deletion des PFV Gag-Proteins vom C-Terminus her zeigte, dass die N-terminalen 300 As von PFV Gag ausreichend für die Freisetzung von partikulärem viralem Proteinmaterial sind. Die Analyse weiterer Deletionsmutanten innerhalb des N-Terminus des PFV Gag-Proteins belegte, dass die As 6 - 200 für die Bildung viraler Kapside entbehrlich sind, aber für die Interaktion mit dem viralen Glykoprotein und für eine Freisetzung der viralen Partikel aus der Wirtszelle essentiell sind. Die Substitution einzelner konservierter Aminosäuren durch Alanin zwischen As 40 - 60 blockierte die Partikelmorphogenese. Die Aminosäureabfolge dieses Proteinabschnittes zeigte eine große Ähnlichkeit mit einem zellulären Transportsignal, dass in den Gag-Proteinen von Retroviren des Typ-D-Morphogeneseweges entdeckt worden ist. Eine parallele Mutationsanalyse des FFV Gag-Proteins ließ vermuten, dass dieses Motiv wohl universell in allen FV Gag-Proteinen vorhanden ist. Weiterhin konnten Aminosäureabschnitte am unmittelbaren N-Terminus des PFV Gag-Proteins sowie zwischen As 130 - 200 eingegrenzt werden, die essentiell für die Struktur des Proteins sind und eventuell eine wichtige Funktion bei der Partikelmorphogenese erfüllen. Weitere Untersuchungen und insbesondere eine Strukturaufklärung des PFV Gag-Proteins sind nötig, um die genaue Funktion der einzelnen Proteinabschnitte zu charakterisieren.

Strahlentherapie im Beckenbereich, wie bei einer Tumortherapie häufig nötig, führt zur Mitbestrahlung der Harnblase. Dieses Normalgewebe zeigt hierbei eine akute und eine späte Strahlenreaktion. Während die akute Strahlenreaktion vollständig reversibel ist, ist die späte Reaktion irreversibel und progradient. Die Strahlenreaktion wurde mittels intravesikaler Zystometrie über das Blasenvolumen ermittelt. Getestet wurden Heparin und PPS als Glykosaminoglykane. Im Rahmen der Arbeit konnte gezeigt werden, dass die akute Strahlenreaktion durch intravesikale Applikation von Glykosaminoglykanen beeinflusst werden kann, und zwar im Sinne einer Reduktion der Reaktion. Die späte Reaktion selbst dagegen nicht. Dafür konnte aber gezeigt werden, dass eine starke konsekutive Komponente der späten Reaktion vorhanden ist. Damit beeinflusst das Maß der akuten Strahlenreaktion die Schwere der späten Reaktion. Eine Verringerung der Reaktionshäufigkeit in der akuten Phase führt zu einer Reduktion der Reaktionshäufigkeit in der Spätphase. / Radiation therapy in the pelvic region leads to a radiation of the bladder too. This normal tissue shows an acute and a late reaction. Whereas the acute one is completely reversible the chronic one is irreversible an progradient. The radiation reaction was measured as a reduction of the volume of the bladder by intravesical cystotonometry. Heparin and PPS were tried as GAG’s. In these examinations could be shown that it is possible to influence the acute reaction by intravesical application of GAG’s . In contrast the chronic phase an influence was impossible. Otherwise it could be proved that there is a high consecutive component in the chronic reaction. That means that a reduction in the frequency of the acute reaction leads to a reduction of the frequency of the chronic reaction.

Where does your food come from? This is a simple question that many people ask but don't truly want to have to answer to. We have some idea of the concept of farming that is cobbled together from images taken from the media and advertisements. The vision of a small pastoral farm where animals roam around in outdoor pens or live in stately wooden barns is the idea that comes to mind when we think of farming. This concept could not be further from the actual truth. This difference between your perception and the reality is due to a widespread effort to block images of modern farming practices from public view. Those orchestrating this deception are so powerful that they have pushed censorship laws onto nineteen different states in the United States. These laws are collectively called the Ag Gag. This series of photographs was created to shed light on modern farming practices and to bring awareness to the overreach of agricultural corporations in dictating laws limiting individual free speech. In this work you see images of what modern large scale animal farming actually looks like. You will also see what impacts this has on the environment and learn about the benefits and problems with this type of farming. In the end the most important question I want you to ask yourself is: Is this where I want my food coming from?

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INTRODUÇÃO: A infecção por HIV-1 é um grave problema de saúde pública causando elevada taxa de morbidade e mortalidade. Entretanto, alguns indivíduos são considerados resistentes à infecção por HIV-1, mesmo após repetidas exposições ao vírus. Vários fatores imunológicos e genéticos podem estar associados a resistência à infecção, como ativação de componentes da imunidade inata e também devido ao baixo perfil de ativação das células T. É possível que nos indivíduos expostos e não infectados por HIV-1 (ENI) ocorra uma importante atuação das células T secretoras de IL-17 e IL-22, e também as células T reguladoras, pois são necessárias para a manutenção e homeostase das mucosas associadas ao intestino (GALT). OBJETIVO: Avaliar o fenótipo e a função de células TCD4+ e TCD8+ em casais sorodiscordante ao HIV-1, compostos por indivíduos ENI e os parceiros infectados por HIV-1. MÉTODOS: Os casais sorodiscordantes ao HIV-1, consistiam de 23 indivíduos expostos não-infectados (ENI), 14 mulheres e 9 homens, com mediana de 41 anos e 21 parceiros infectados por HIV-1 (HIV), 20 homens e 1 mulher com mediana de 41 anos. Os controles saudáveis foram 24 indivíduos (14 mulheres e 10 homens) com mediana de 37 anos. Os casais sorodiscordantes foram compostos por 16 heterossexuais e 7 homossexuais, com tempo de relacionamento de 13 anos. As frequências de células Th17, Th22 e Tc22, as células T polifuncionais foram analisadas em células mononucleares (CMNs) do sangue periférico, estimulados com peptídeos da região Gag do HIV-1 e da enterotoxina B do Staphylococcus aureus (SEB), a frequência de células T reguladoras, o perfil fenotípico de exaustão/diferenciação e a expressão da integrina alfa4?7 e CCR9 em células T, foram realizados por citometria de fluxo. RESULTADOS: No grupo HIV, as células T CD4+ e CD8+ do sangue periférico mostrou maior frequência de CD95 e PD-1 e baixa expressão de CD127 comparado ao grupo ENI e controle. A frequência de células Th17 em CMNs aumentou nos grupos ENI e HIV-1 na condição sem estímulo, contudo, após estímulo com os peptídeos da região p24 da Gag do HIV-1 induziu resposta somente no grupo HIV-1. O grupo ENI mostrou resposta antígeno-especifica somente para IL-22. Além disto, avaliando as células Tc22 e Th22, foi verificado aumento da resposta aos peptídeos da Gag e também ao SEB, nos grupos HIV e ENI. A presença de células T polifuncionais antígeno-especificas, secretoras de 5-4 citocinas, foi detectada apenas em células T CD38+ no grupo HIV, enquanto os indivíduos ENI mostraram resposta polifuncional por células T CD38- somente ao estímulo policlonal por SEB. Uma diminuição do número absoluto de células T reguladoras (CD4+CD25+CD127low/-Foxp3+) foi detectada no grupo HIV comparado ao ENI e controle, com maior expressão de moléculas HLA-DR e CD95. Além disto, foi detectado diminuição na frequência de células TCD8+ ?4?7+ no grupo ENI e de células TCD4+ alfa4beta7+ nos grupos ENI e HIV. Houve uma correlação positiva entre as células Tc22 e Th22 com as células TCD8+ e TCD4+ que expressam alfa4beta7, no grupo ENI e HIV-1. CONCLUSÃO: Os indivíduos ENI são capazes de desenvolver resposta antígeno-específicas relacionadas com a IL-22, que possui importante função na imunidade de mucosas. Além disto, mostram presença de células T polifuncionais com baixo perfil de ativação a estímulo policlonal. Os dados evidenciam que os indivíduos ENI, mostram indução de células Tc22, aumento de expressão de moléculas de migração para o intestino e equilíbrio entre as células efetoras e Treg, que em conjunto, devem exercer importante papel para a resistência à infecção por HIV-1 / INTRODUCTION: The HIV-1 infection is a major public health problem causing high morbidity and mortality. However, some individuals are considered resistant to HIV-1 infection even after repeated HIV-1 exposures. Several immunologic and genetic factors could be associated with the resistance to infection, such as activation of innate immunity components and due to the low profile of T-cell activation. It is possible that in HIV-1 exposed uninfected individuals (EU) occurs an important activity of the T cells secreting IL-17 and IL-22, including regulatory T cells, which are necessary to maintenance of homeostasis of gut-associated lymphoid tissue (GALT). AIM: To evaluate the phenotype and function of CD4+ and CD8+ T cells in HIV-1-serodiscordant couples, composed by the EU individuals and the infected HIV-1 partners. METHODS: The HIV-1-serodiscordant couples consisted of 23 EU individuals, 14 women and 9 men, with a median age of 41 years and 21 partners infected by HIV-1, 20 men and 1 woman, with a median of 41 years. Healthy controls consisted of 24 individuals (14 women and 10 men) with a median age of 37 years. The serodiscordant couples were composed by 16 homosexuals and 7 heterosexuals, reporting a median relationship duration of 13 years with a single partner. The frequency of Th17, Th22 and Tc22 cells, the polyfunctional T cells were assessed in mononuclear cells (MNCs) from peripheral blood, stimulated with the peptides from the gag region of HIV-1 and enterotoxin B from Staphylococcus aureus (SEB), the frequency of regulatory T cells and the exhaustion/differentiation phenotypic profile and expression of integrin alfa4beta7 and CCR9 in T cells were assessed by flow cytometry. RESULTS: In HIV group, CD4+ and CD8+ T cells from peripheral blood showed a higher frequency of PD-1, and CD95 and low expression of CD127 compared to ENI and control groups. The frequency of Th17 cells in MNCs increased in ENI and HIV-1 groups in the unstimulated conditions, however, upon stimulation with p24 peptides of HIV-1 Gag induced response only in HIV-1 group. The ENI group showed antigen-specific response only for IL-22. Moreover, evaluating the Tc22 and Th22 cells, it was found increased response to Gag peptides and also for SEB in both, HIV and ENI groups. The presence of polyfunctional antigen-specific T cells secreting 5-4 cytokines, was only detected in CD38+ T cells from HIV group, while ENI individuals showed polyfunctional CD38- T cells response only with the polyclonal stimulus with SEB. A decreased absolute number of regulatory T cells (CD4 + CD25 + CD127low /-Foxp3 +) was detected in HIV group compared to the EU and control groups, with higher expression of HLA-DR and CD95 molecules. In addition, it was detected decreased frequency of CD8+ alfa4beta7 + T cells in the ENI group and CD4+ alfa4beta7+ T cells in both, ENI and HIV groups. There was a positive correlation between Tc22 and Th22 cells with the CD8+ and CD4+ T cells expressing alfa4beta7, in the ENI and HIV-1 groups. CONCLUSION: The EU individuals are able to develop antigen-specific response related to IL-22, which has an important function in the mucosal immunity. In addition, showed presence of polyfunctional T cells with low activation profile to polyclonal stimuli. The data show that the EU individuals, showed induction of Tc22 cells, increased expression of homing molecules into the intestine and balance between effector cells and Treg cells, which together, must play an important role in the HIV-1 resistance

INTRODUÇÃO: A infecção por HIV-1 é um grave problema de saúde pública causando elevada taxa de morbidade e mortalidade. Entretanto, alguns indivíduos são considerados resistentes à infecção por HIV-1, mesmo após repetidas exposições ao vírus. Vários fatores imunológicos e genéticos podem estar associados a resistência à infecção, como ativação de componentes da imunidade inata e também devido ao baixo perfil de ativação das células T. É possível que nos indivíduos expostos e não infectados por HIV-1 (ENI) ocorra uma importante atuação das células T secretoras de IL-17 e IL-22, e também as células T reguladoras, pois são necessárias para a manutenção e homeostase das mucosas associadas ao intestino (GALT). OBJETIVO: Avaliar o fenótipo e a função de células TCD4+ e TCD8+ em casais sorodiscordante ao HIV-1, compostos por indivíduos ENI e os parceiros infectados por HIV-1. MÉTODOS: Os casais sorodiscordantes ao HIV-1, consistiam de 23 indivíduos expostos não-infectados (ENI), 14 mulheres e 9 homens, com mediana de 41 anos e 21 parceiros infectados por HIV-1 (HIV), 20 homens e 1 mulher com mediana de 41 anos. Os controles saudáveis foram 24 indivíduos (14 mulheres e 10 homens) com mediana de 37 anos. Os casais sorodiscordantes foram compostos por 16 heterossexuais e 7 homossexuais, com tempo de relacionamento de 13 anos. As frequências de células Th17, Th22 e Tc22, as células T polifuncionais foram analisadas em células mononucleares (CMNs) do sangue periférico, estimulados com peptídeos da região Gag do HIV-1 e da enterotoxina B do Staphylococcus aureus (SEB), a frequência de células T reguladoras, o perfil fenotípico de exaustão/diferenciação e a expressão da integrina alfa4?7 e CCR9 em células T, foram realizados por citometria de fluxo. RESULTADOS: No grupo HIV, as células T CD4+ e CD8+ do sangue periférico mostrou maior frequência de CD95 e PD-1 e baixa expressão de CD127 comparado ao grupo ENI e controle. A frequência de células Th17 em CMNs aumentou nos grupos ENI e HIV-1 na condição sem estímulo, contudo, após estímulo com os peptídeos da região p24 da Gag do HIV-1 induziu resposta somente no grupo HIV-1. O grupo ENI mostrou resposta antígeno-especifica somente para IL-22. Além disto, avaliando as células Tc22 e Th22, foi verificado aumento da resposta aos peptídeos da Gag e também ao SEB, nos grupos HIV e ENI. A presença de células T polifuncionais antígeno-especificas, secretoras de 5-4 citocinas, foi detectada apenas em células T CD38+ no grupo HIV, enquanto os indivíduos ENI mostraram resposta polifuncional por células T CD38- somente ao estímulo policlonal por SEB. Uma diminuição do número absoluto de células T reguladoras (CD4+CD25+CD127low/-Foxp3+) foi detectada no grupo HIV comparado ao ENI e controle, com maior expressão de moléculas HLA-DR e CD95. Além disto, foi detectado diminuição na frequência de células TCD8+ ?4?7+ no grupo ENI e de células TCD4+ alfa4beta7+ nos grupos ENI e HIV. Houve uma correlação positiva entre as células Tc22 e Th22 com as células TCD8+ e TCD4+ que expressam alfa4beta7, no grupo ENI e HIV-1. CONCLUSÃO: Os indivíduos ENI são capazes de desenvolver resposta antígeno-específicas relacionadas com a IL-22, que possui importante função na imunidade de mucosas. Além disto, mostram presença de células T polifuncionais com baixo perfil de ativação a estímulo policlonal. Os dados evidenciam que os indivíduos ENI, mostram indução de células Tc22, aumento de expressão de moléculas de migração para o intestino e equilíbrio entre as células efetoras e Treg, que em conjunto, devem exercer importante papel para a resistência à infecção por HIV-1 / INTRODUCTION: The HIV-1 infection is a major public health problem causing high morbidity and mortality. However, some individuals are considered resistant to HIV-1 infection even after repeated HIV-1 exposures. Several immunologic and genetic factors could be associated with the resistance to infection, such as activation of innate immunity components and due to the low profile of T-cell activation. It is possible that in HIV-1 exposed uninfected individuals (EU) occurs an important activity of the T cells secreting IL-17 and IL-22, including regulatory T cells, which are necessary to maintenance of homeostasis of gut-associated lymphoid tissue (GALT). AIM: To evaluate the phenotype and function of CD4+ and CD8+ T cells in HIV-1-serodiscordant couples, composed by the EU individuals and the infected HIV-1 partners. METHODS: The HIV-1-serodiscordant couples consisted of 23 EU individuals, 14 women and 9 men, with a median age of 41 years and 21 partners infected by HIV-1, 20 men and 1 woman, with a median of 41 years. Healthy controls consisted of 24 individuals (14 women and 10 men) with a median age of 37 years. The serodiscordant couples were composed by 16 homosexuals and 7 heterosexuals, reporting a median relationship duration of 13 years with a single partner. The frequency of Th17, Th22 and Tc22 cells, the polyfunctional T cells were assessed in mononuclear cells (MNCs) from peripheral blood, stimulated with the peptides from the gag region of HIV-1 and enterotoxin B from Staphylococcus aureus (SEB), the frequency of regulatory T cells and the exhaustion/differentiation phenotypic profile and expression of integrin alfa4beta7 and CCR9 in T cells were assessed by flow cytometry. RESULTS: In HIV group, CD4+ and CD8+ T cells from peripheral blood showed a higher frequency of PD-1, and CD95 and low expression of CD127 compared to ENI and control groups. The frequency of Th17 cells in MNCs increased in ENI and HIV-1 groups in the unstimulated conditions, however, upon stimulation with p24 peptides of HIV-1 Gag induced response only in HIV-1 group. The ENI group showed antigen-specific response only for IL-22. Moreover, evaluating the Tc22 and Th22 cells, it was found increased response to Gag peptides and also for SEB in both, HIV and ENI groups. The presence of polyfunctional antigen-specific T cells secreting 5-4 cytokines, was only detected in CD38+ T cells from HIV group, while ENI individuals showed polyfunctional CD38- T cells response only with the polyclonal stimulus with SEB. A decreased absolute number of regulatory T cells (CD4 + CD25 + CD127low /-Foxp3 +) was detected in HIV group compared to the EU and control groups, with higher expression of HLA-DR and CD95 molecules. In addition, it was detected decreased frequency of CD8+ alfa4beta7 + T cells in the ENI group and CD4+ alfa4beta7+ T cells in both, ENI and HIV groups. There was a positive correlation between Tc22 and Th22 cells with the CD8+ and CD4+ T cells expressing alfa4beta7, in the ENI and HIV-1 groups. CONCLUSION: The EU individuals are able to develop antigen-specific response related to IL-22, which has an important function in the mucosal immunity. In addition, showed presence of polyfunctional T cells with low activation profile to polyclonal stimuli. The data show that the EU individuals, showed induction of Tc22 cells, increased expression of homing molecules into the intestine and balance between effector cells and Treg cells, which together, must play an important role in the HIV-1 resistance