RESUMEN
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.
Asunto(s)
Infecciones por VIH/complicaciones , Infecciones por VIH/inmunología , VIH-1/inmunología , Complicaciones Infecciosas del Embarazo/inmunología , Subgrupos de Linfocitos T/inmunología , Adulto , Estudios de Casos y Controles , Femenino , Antígenos VIH/administración & dosificación , Infecciones por VIH/transmisión , Infecciones por VIH/virología , VIH-1/fisiología , Humanos , Técnicas In Vitro , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Interleucina-10/biosíntesis , Activación de Linfocitos , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Subgrupos de Linfocitos T/virología , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/virología , Replicación Viral/inmunología , Adulto JovenRESUMEN
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.