Five chromosome segregation in polar bodies and the corresponding oocyte.

For a comprehensive picture of the meiotic process and to follow up its products, five chromosomes were tested by fluorescent in-situ hybridization in both polar bodies (PB) and corresponding 145 oocytes. Results were obtained in 143 sets and the prediction of euploidy or aneuploidy based on PB analysis was confirmed by direct analysis in 140 oocytes (98%). Concordance for all chromosomes was found in 132 oocytes, while in the remaining eight, at least one chromosome did not reflect the prediction made by the corresponding PB. When restricting the analysis to the 132 fully concordant oocytes, 215 errors were found in PB: 58% in PB1 and 42% in PB2. Premature separation of chromatids occurred in 89% of aneuploid PB1, whereas only 11% of errors derived from bivalent non-disjunction. In 19% of meiosis-I errors, a complementary error in meiosis II compensated the error originated in the first meiotic division. In conclusion, the testing of PB predicted reliably the oocyte's chromosome condition. Although limited to five chromosomes, the follow up of meiosis by fluorescent in-situ hybridization provided a full description of chromosome allocation during the two divisions characterizing the nuclear maturation of the oocyte.

T lymphocyte maturation is impaired in healthy young individuals carrying trisomy 21 (Down syndrome).

Cytokine production, immune activation, T lymphocytes maturation, and serum IL-7 concentration were examined in 24 youngsters with Down syndrome and no acquired diseases (healthy Down syndrome [12 prepubertal, 13 pubertal]) and 42 age- and gender-matched controls (20 prepubertal, 22 pubertal). Results showed that a complex immune and impairment is present in healthy individuals with Down syndrome in whom interferon gamma, interleukin (IL) IL-10 production, as well as serum IL-7 concentrations and activation markers-bearing T lymphocytes were significantly augmented. Additionally, a complex skewing of post-thymic lymphocyte maturation pathways was observed in patients: significant reduction of CD4+ and CD8+ naive (RA+CCR7+) lymphocytes, significant increase of CD4+ and CD8+ central memory (RA-CCR7+), and terminally differentiated (TD) (RA+CCR7-) lymphocytes.

Humoral and cellular response to influenza vaccine in HIV-infected children with full viroimmunologic response to antiretroviral therapy.

OBJECTIVE: It is unclear whether the ability to respond to vaccines is restored by antiretroviral therapy. We evaluated the influenza-specific immune responses elicited by a virosomal vaccine in HIV-infected children on long-term successful highly active antiretroviral therapy (HAART). METHODS: This was an observational, prospective, open-label study enrolling 24 HIV-infected, HAART-treated (85 months' mean exposure), vaccine-naive children (median age=11.9 years) and 14 age- and gender-matched healthy controls. Mean CD4 T-cell counts (>900 cells/microL) and percentages (>37%) were comparable. The HIV RNA level was <50 copies/mL in all patients. Children received a single dose of trivalent virosome-adjuvanted influenza vaccine. A/H3N2-, A/H1N1-, and B-antigen-specific antibody (Ab) titers and subclasses and vaccine-specific interferon-gamma (IFNgamma)- and interleukin (IL)-2-producing T lymphocytes were analyzed at baseline and 1 and 6 months after immunization. RESULTS: Seroconversion (>or=4-fold Ab titer raise in >40% of patients) and seroprotection (Ab titer>or=1:40 in >70% of patients) was achieved at 1 month in both groups; however, fewer HIV-infected children fulfilled these criteria. The A/H3N2- and A/H1N1-specific Ab geometric mean titers were lower in HIV-infected children compared with healthy controls at 1 and 6 months; interestingly, a boost in vaccine-specific IgG3 T helper 1 type Ab was seen in healthy controls alone. Finally, vaccine specific-IFNgamma- and IL-2-producing T lymphocytes were reduced at both time points in HIV-infected children compared with healthy controls. CONCLUSIONS: One injection of virosomal-adjuvanted influenza vaccine stimulates good immune responses, although the humoral and cellular immune responses are reduced in HIV-infected children compared to healthy children. This indicates that immunologic function impairments may persist upon HIV infection even if HIV-positive viremia is suppressed and immune recovery seems to be achieved.

The mucosae-associated epithelial chemokine (MEC/CCL28) modulates immunity in HIV infection.

BACKGROUND: CCL28 (MEC) binds to CCR3 and CCR10 and recruits IgA-secreting plasma cells (IgA-ASC) in the mucosal lamina propria (MLP). Mucosal HIV-specific IgA are detected in HIV-infection and exposure. The CCL28 circuit was analyzed in HIV-infected and-exposed individuals and in HIV-unexposed controls; the effect of CCL28 administration on gastrointestinal MLP IgA-ASC was verified in a mouse model. METHODOLOGY/FINDINGS: CCL28 was augmented in breast milk (BM) plasma and saliva of HIV-infected and -exposed individuals; CCR3+ and CCR10+ B lymphocytes were increased in these same individuals. Additionally: 1) CCL28 concentration in BM was associated with longer survival in HIV vertically-infected children; and 2) gastro-intestinal mucosal IgA-ASC were significantly increased in VSV-immunized mice receiving CCL28. CONCLUSIONS: CCL28 mediates mucosal immunity in HIV exposure and infection. CCL28-including constructs should be considered in mucosal vaccines to prevent HIV infection of the gastro-intestinal MLP via modulation of IgA-ASC.

An immunological comparison of third companion in advanced drug-naive HIV-infected patients.

An immunological comparison of three different third companions (abacavir [ABC], efavirenz [EFV], ritonavir-boosted indinavir [IDVr]) on a backbone of either zidovudine plus didanosine (AZT/ddI) or zidovudine plus lamivudine (AZT/3TC) was performed in 76 HIV-infected, advanced-naive patients. Baseline median CD4 count and viremia were 217/microL and 238,301 copies/mL, respectively. Immunologic parameters were measured at baseline and after months of therapy. By the end of the study, 36 patients (mostly in the protease inhibitor [PI]-containing arms) had dropped out of the study; 22/36 cases of drop out were due to tolerability issues. All regimens resulted in increases in CD4 counts, with the most solid changes seen in patients using ABC as a third companion. Median HIV plasma viremia at month 12 was <50 copies/mL, and viremia was undetectable in 26/38 patients (68%). At the end of the study period, HIV antigen- and mitogen-stimulated proliferation overall was better in patients using either of the PI-boosted third companions. In these patients, the strongest down-modulation of activation marker-bearing cells was also observed. Finally, CD8+/28-/CD45RA+ lymphocytes (effector cells) were increased in all groups of patients with the exception of individuals receiving PI-boosted therapies. Results of this pilot study, although very preliminary, suggest that different combinations of antivirals result in a range of effects on immune cell functions. The clinical implications of these results need to be further analyzed in follow-up studies and in larger cohorts of patients.

Low interleukin-10 production is associated with diabetes in HIV-infected patients undergoing antiviral therapy.

Reduced interleukin-10 (IL-10) production is associated with type 2 diabetes in elderly individuals. Antiviral therapy (ARV)-induced immune modulation results in diminished IL-10 production, and diabetes can be observed in ARV-treated human immunodeficiency virus (HIV)-infected individuals. We analyzed, in a cross-sectional pilot study, HIV-antigen-stimulated IL-10 and tumor necrosis factor alpha (TNFalpha) production, and intracellular concentration (ICC), as well as B7-H1 expression, a marker preferentially presented by IL-10-producing cells, in 20 ARV-treated individuals in whom diabetes did (n=10; diabetes mellitus, DM) or did not (n=10; controls) develop. Pre-ARV glucose, cholesterol, and triglycerides levels, duration of HIV infection and of therapy, exposure to protease inhibitors (PI), HIV plasma viremia, CD4 counts, and nadir were similar in DM and control patients. Results showed that: (1) IL-10 production was lower; (2) IL-10 ICC was reduced; (3) B7-H1-expressing CD19(+) cells were diminished; and (4) TNFalpha production and ICC by CD4(+) T cells was augmented in DM patients. Development of diabetes in HIV infected, ARV-treated individuals could be a response to therapy. Similar to what is observed in elderly individuals, low IL-10 production is associated with diabetes in antiviral-treated HIV infection. Further studies will be necessary to clarify whether low IL-10 is a risk factor for, or a consequence of, diabetes.