ABSTRACT
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.
Subject(s)
HIV Infections/complications , HIV Infections/immunology , HIV-1/immunology , Pregnancy Complications, Infectious/immunology , T-Lymphocyte Subsets/immunology , Adult , Case-Control Studies , Female , HIV Antigens/administration & dosage , HIV Infections/transmission , HIV Infections/virology , HIV-1/physiology , Humans , In Vitro Techniques , Infant, Newborn , Infectious Disease Transmission, Vertical/prevention & control , Interleukin-10/biosynthesis , Lymphocyte Activation , Pregnancy , Pregnancy Complications, Infectious/virology , T-Lymphocyte Subsets/virology , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/virology , Virus Replication/immunology , Young AdultABSTRACT
This work aimed to evaluate immune events in HIV-1-exposed uninfected neonates born from mothers who control (G1) or not (G2) the plasma viral load, using unexposed neonates as controls. Cord blood from each neonate was collected, plasma and mononuclear cells were separated and the lymphoproliferation and cytokine pattern were evaluated. The results demonstrated that the in vitro lymphoproliferation induced by polyclonal activators was higher in the G2 neonates. Nevertheless, no cell culture responded to poll synthetic HIV-1 envelope peptides. The cytokine dosage in the plasma and supernatants of polyclonally-activated cultures demonstrated that, while IL-4 and IL-10 were the dominant cytokines produced in G1 and control groups, IFN-gamma and TNF-alpha were significantly higher in G2 neonates. Systemic levels of IL-10 observed among the G1 neonates were higher in those born from anti-retroviral treated mothers. In summary, our results indicate an altered immune responsiveness in neonates exposed in utero to HIV and support the role of maternal anti-retroviral treatment to attenuate it.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , HIV Infections/immunology , HIV-1/immunology , Adult , Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/virology , CD8-Positive T-Lymphocytes/virology , Cell Proliferation , Female , HIV Antigens/immunology , HIV Infections/drug therapy , HIV Infections/virology , HIV-1/metabolism , Humans , Immunity, Maternally-Acquired , Infant, Newborn , Infectious Disease Transmission, Vertical , Interferon-gamma/immunology , Interferon-gamma/metabolism , Interleukin-10/immunology , Interleukin-10/metabolism , Interleukin-4/immunology , Interleukin-4/metabolism , Lymphocyte Activation , Tumor Necrosis Factor-alpha/immunology , Tumor Necrosis Factor-alpha/metabolism , Viral LoadABSTRACT
OBJECTIVE: To evaluate the impact of age on the proliferative response, cytokine profile and viral kinetics in AIDS patients treated successfully with antiretroviral drugs. METHODS: Peripheral blood mononuclear cells (PBMC), CD4 cell-depleted PBMC or CD4 T cells from young adult and aged HIV-1-infected patients were activated in vitro with anti-CD3 with or without interleukin (IL)-2. Lymphoproliferation and cytokines were measured after 3 days and in-vitro HIV-1 replication after 7 days. RESULTS: Both lymphoproliferation and cytokine [IL-1beta, tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma)] secretion were higher in younger than in older AIDS patients. In cultures of cells derived from aged patients and activated by anti-CD3, IFN-gamma production was severely damage and IL-10 production was much higher. Although IL-2 addition to activated PBMC elevated IFN-gamma secretion, IL-10 production remained elevated in the aged group. The depletion of CD4 T lymphocytes from these cultures dramatically reduced released IL-10 in the older group but did not alter significantly IFN-gamma production. Interestingly, higher IL-10 levels produced by CD4 T cells were related to lower in-vitro HIV-1 replication, and the blockade of this cytokine by anti-IL-10 monoclonal antibody enhanced virus replication. This effect may be correlated with elevated TNF-alpha secretion. Finally, impaired IFN-gamma secretion detected in activated CD4 T cells obtained from aged patients was not directly correlated with high IL-10 production. CONCLUSIONS: Elevated IL-10 production by aged AIDS patients contributed considerably to control of HIV replication and to inhibition of TNF-alpha secretion but not to the reduced IFN-gamma production.
