Background In utero transmission of HIV-1 occurs on average in only 3%–15% of HIV-1-exposed neonates born to mothers not on antiretroviral drug therapy. Thus, despite potential exposure, the majority of infants remain uninfected. Weak HIV-1-specific T-cell responses have been detected in children exposed to HIV-1, and potentially contribute to protection against infection. We, and others, have recently shown that the removal of CD4+CD25+ T-regulatory (Treg) cells can reveal strong HIV-1 specific T-cell responses in some HIV-1 infected adults. Here, we hypothesized that Treg cells could suppress HIV-1-specific immune responses in young children.Methodology/Principal FindingsWe studied two cohorts of children. The first group included HIV-1-exposed-uninfected (EU) as well as unexposed (UNEX) neonates. The second group comprised HIV-1-infected and HIV-1-EU children. We quantified the frequency of Treg cells, T-cell activation, and cell-mediated immune responses. We detected high levels of CD4+CD25+CD127− Treg cells and low levels of CD4+ and CD8+ T cell activation in the cord blood of the EU neonates. We observed HIV-1-specific T cell immune responses in all of the children exposed to the virus. These T-cell responses were not seen in the cord blood of control HIV-1 unexposed neonates. Moreover, the depletion of CD4+CD25+ Treg cells from the cord blood of EU newborns strikingly augmented both CD4+ and CD8+ HIV-1-specific immune responses.Conclusions/SignificanceThis study provides new evidence that EU infants can mount strong HIV-1-specific T cell responses, and that in utero CD4+CD25+ T-regulatory cells may be contributing to the lack of vertical transmission by reducing T cell activation.

Both systemic lupus erythematosus (SLE) and its treatment can cause immunosuppression and a decreased response to vaccination. We evaluated 30 children and adolescents with SLE, and 14 age-matched healthy subjects (control group) regarding immunophenotyping and lymphocyte apoptosis by flow cytometry, while measles and tetanus antibodies were measured by enzyme-linked immunosorbent assay (ELISA). The SLE group was divided according to disease activity into inactive SLE and active SLE. Individuals with active SLE had lower CD4+ T and natural killer (NK) cells/mm(3) than the control group. Active and inactive SLE individuals had more CD38 molecules/CD8+ T cells and more CD4+ T, CD8+ T and B cells in apoptosis (as assessed by caspase-3 expression) than the control group. Patients with active SLE had a diminished CD28 expression on both CD4+ T and on CD8+ T cells and a higher CD86 expression on B cells than the control group. Measles antibody levels in the SLE groups were similar to the control group. In contrast, tetanus antibody levels were lower in the SLE groups than in the control group. The latter also directly correlated with the CD4+ T-cell and NK-cell counts from SLE patients (regression coefficient, 2.686 and 1.782; p = 0.010 and p = 0.039, respectively). We concluded that despite being up-to-date for tetanus vaccine, SLE patients presented with a poor immune response to tetanus vaccine.

Lymphocyte subsets, activation markers and apoptosis were assessed in 20 HIV-exposed noninfected (ENI) children born to HIV-infected women who were or not exposed to antiretroviral (ARV) drugs during pregnancy and early infancy. ENI children and adolescents were aged 6-18 years and they were compared to 25 age-matched healthy non-HIV-exposed children and adolescents (Control). ENI individuals presented lower CD4(+) T cells/mm(3) than Control group (control: 1120.3 vs. ENI: 876.3; t-test, p = 0.030). ENI individuals had higher B-cell apoptosis than Control group (Control: 36.6%, ARV exposed: 82.3%, ARV nonexposed: 68.5%; Kruskal-Wallis, p < 0.05), but no statistical difference was noticed between those exposed and not exposed to ARV. Immune activation in CD4(+) T, CD8(+) T and in B cells was comparable in ENI and in Control children and adolescents. Subtle long-term immune alterations might persist among ENI individuals, but the clinical consequences if any are unknown, and these children require continued monitoring.

In an era when natural boosters are less frequent, an immune surveillance might be necessary to investigate waning immunity as occurs for tetanus.

Immunological and clinical findings suggestive of some immune dysfunction have been reported among HIV-exposed uninfected (HEU) children and adolescents. Whether these defects are persistent or transitory is still unknown. HEU pediatric population at birth, 12 months, 6-12 years were evaluated in comparison to healthy age-matched HIV-unexposed controls. Plasma levels of LPS, sCD14, cytokines, lymphocyte immunophenotyping and T-cell receptor excision circles (TREC) were assessed. HEU and controls had similar LPS levels, which remained low from birth to 6-12 years; for plasma sCD14, IL-2, IL-6, IL-7, IL-10, IL-12p70, IL-13, IL-17, IFN-γ, TNF-α, G-CSF, GM-CSF and MCP-1, which increased from birth to 12 months and then decreased at 6-12 years; and for TREC/106 PBMC at birth in HEU and controls. By contrast, plasma MIP-1β levels were lower in HEU than in controls (p=0.009) at 12 months, and IL-4 levels were higher in HEU than controls (p=0.04) at 6-12 years. Immune activation was higher in HEU at 12 months and at 6-12 years than controls based on frequencies of CD38+HLA-DR+CD8+T cells (p=0.05) and of CD38+HLA-DR+CD4+T cells (p=0.006). Resting memory and activated mature B cells increased from birth to 6-12 years in both groups. The development of the immune system in vertically HEU individuals is comparable to the general population in most parameters, but subtle or transient differences exist. Their role in influencing clinical incidences in HEU is unknown.