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
This work aims to elucidate the effects of age and HIV-1 infection on the frequency and function of T cell subsets in response to HIV-specific and non-specific stimuli. As compared with the younger AIDS group, the frequencies of naive and central memory T cells were significantly lower in aged AIDS patients. Although there was also a dramatic loss of classical CD4(+)FoxP3(+)CD25(+)Treg cells in this patient group, high frequencies of IL-10-producing CD4(+)FoxP3(-) T cells were observed. In our system, the increased production of IL-10 in aged AIDS patients was mainly derived from Env-specific CD4(+)FoxP3(-)CD152(+) T cells. Interestingly, while the blockade of IL-10 activity by monoclonal antibody clearly enhanced the release of IL-6 and IL-1ß by Env-stimulated PBMC cultures from aged AIDS patients, this monoclonal antibody enhanced in vitro HIV-1-replication. In conclusion, HIV infection and aging undoubtedly contribute synergistically to a complex immune dysfunction in T cell compartment of HAART-treated older HIV-infected individuals.
