RESUMO
Evidences indicate that pregnancy can alter the Ag-specific T-cell responses. This work aims to evaluate the impact of pregnancy on the in vitro HIV-1-specific immune response. As compared with non-pregnant patients, lower T-cell proliferation and higher IL-10 production were observed in T-cell cultures from pregnant patients following addition of either mitogens or HIV-1 antigens. In our system, the main T lymphocyte subset involved in producing IL-10 was CD4(+)FoxP3(-). Depletion of CD4(+) cells elevated TNF-α and IFN-γ production. Interestingly, the in vitro HIV-1 replication was lower in cell cultures from pregnant patients, and it was inversely related to IL-10 production. In these cultures, the neutralization of IL-10 by anti-IL-10 mAb elevated TNF-α release and HIV-1 replication. In conclusion, our results reveal that pregnancy-related events should favor the expansion of HIV-1-specific IL-10-secreting CD4(+) T-cells in HIV-1-infected women, which should, in the scenario of pregnancy, help to reduce the risk of vertical HIV-1 transmission.
Assuntos
Infecções por HIV/complicações , Infecções por HIV/imunologia , HIV-1/imunologia , Complicações Infecciosas na Gravidez/imunologia , Subpopulações de Linfócitos T/imunologia , Adulto , Estudos de Casos e Controles , Feminino , Antígenos HIV/administração & dosagem , Infecções por HIV/transmissão , Infecções por HIV/virologia , HIV-1/fisiologia , Humanos , Técnicas In Vitro , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Interleucina-10/biossíntese , Ativação Linfocitária , Gravidez , Complicações Infecciosas na Gravidez/virologia , Subpopulações de Linfócitos T/virologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/virologia , Replicação Viral/imunologia , Adulto JovemRESUMO
Our objective was to evaluate the in vitro functional profile of T cells from uninfected neonates born from HIV-1-infected pregnant women who controlled (G1) or not (G2) the virus replication. We demonstrated that the lymphoproliferation of T cell to polyclonal activators was higher in the G2 as compared with G1. Nevertheless, no detectable proliferative response was observed in response to HIV-1 antigens in both neonate groups. Cytokine dosage in the supernatants of these polyclonally activated T cell cultures demonstrated that, while IL-10 was the dominant cytokine produced in G1, Th17-related cytokines were significantly higher in G2 neonates. The higher Th17 phenotype tendency in G2 was related to high production of IL-23 by lipopolysaccharide-activated monocyte-derived dendritic cells from these neonates. Our results demonstrated immunological disorders in uninfected neonates born from viremic HIV-1-infected mothers that can help to explain why some of these children have elevated risk of clinical morbidity and mortality due to pathological hypersensitivity.