Influência das alterações imunes em gestantes infectadas pelo HIV-1 no perfil funcional das células T de neonatos não infectados

• Ano de defesa: 2013
• Autor(a) principal: Machado, Joana Hygino da Silva
• Orientador(a): Andrade, Arnaldo Feitosa Braga de
• Banca de defesa: Hirata Júnior, Raphael , Tavares, Daniel Augusto Gonçalves , Costilla, Landi Veivi Guillermo , Morgado, Mariza Gonçalves , Pinheiro, Roberta Olmo
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade do Estado do Rio de Janeiro
• Programa de Pós-Graduação: Programa de Pós-Graduação em Microbiologia
• Departamento: Centro Biomédico::Faculdade de Ciências Médicas
• País: BR
• Palavras-chave em Português: HIV; Gravidez; Neonato; Terapia antirretroviral; Citocinas; IL-10; IL-17; IFN-γ; HIV (Vírus); Recém-nascidos; Transmissão vertical de doença infecciosa; Agentes antirretrovirais; Células T; Resposta imune; Carga viral
• Palavras-chave em Inglês: HIV; Pregnant women; Neonate; Anti-retroviral therapy; Cytokines; IL-10; IL-17; IFN-γ
• Área do conhecimento CNPq: CNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIA
• Link de acesso: http://www.bdtd.uerj.br/handle/1/14360

The number of HIV-1-infected young women has been increasing since the beginning of the AIDS epidemic, mainly in developing countries, where the frequency of pregnancy among them is also elevated. The development of strategies for vertical transmission avoidance has enhanced the number of uninfected neonates born from infected mothers. The objective of the present study was to evaluate, in vivo and in vitro, the cytokine profile of uninfected neonates born from pregnant women infected with HIV-1.The results demonstrated high levels of proinflammatory cytokines related to Th17 phenotype associated with low IL-10 production, in plasma as well as in culture supernatants of activated T cells obtained from umbilical cord blood of neonates born from mothers infected with HIV -1 with plasma viral load (PVL) detectable.Interestingly, a similar pro-inflammatory cytokine profile was observed in peripheral blood samples from their respective mothers.On the other hand, high levels of IL-10 associated to reduced production of inflammatory cytokines were measured in blood and in the supernatants of activated T cells culturesfrom women that controlled the PVL, as well as their neonates.Regarding the phenotypic profile of pregnant women infected of HIV-1, the main T lymphocyte subset involved in producing IL-10 was CD4+Foxp3-. Interestingly, the in vitro HIV-1 replication was lower in cell cultures from pregnant patients, and it was related to the inhibitory effects of IL-10 on the production of TNF-α. Finally, ART-in utero-exposed neonates showed to be born with lower weight, and it was inversely correlated with maternal peripheral TNF-α level. In conclusion, the results suggest that pregnant women that are able to control the PVL, and the increment in the production of IL-10 may favor maternal Tr-1 cell expansion, which could help to reduce the risk of vertical transmission of HIV-1 by reducing the rate of viral replication.However, other results also presented here, although preliminary, have revealed adverse effects of viral replication, as well as the use of ART by pregnant women infected with HIV-1 in the development of functional T cells from uninfected newborns.These data may help to explain why some of these children have elevated risk of clinical morbidity and mortality due to a baseline state of pathological hypersensitivity.