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Daria Trabattoni

Publications and source records attributed to Daria Trabattoni.

At least 19 recordsLinked to original sources
PubMed2007

Immune activation and normal levels of endogenous antivirals are seen in healthy adolescents born of HIV-infected mothers.

Immunological analyses performed in healthy adolescents born of HIV-infected (seroreverters) or healthy mothers (healthy controls; HC) showed that immune activation and a skewing of postthymic differentiation are present in adolescent seroreverters. In-utero HIV exposure results in long-lasting imprinting on the immune system. Alternatively, an immune response naturally more prone to activation could prevent vertical infection. Endogenous antivirals (APOBEC, TRIM5alpha) were comparable in seroreverters and HC, and might not play a role in resistance to vertical HIV infection.

Adolescent↗
PubMed2007

IL-22 participates in an innate anti-HIV-1 host-resistance network through acute-phase protein induction.

Certain individuals are resistant to HIV-1 infection, despite repeated exposure to the virus. Although protection against HIV-1 infection in a small proportion of Caucasian individuals is associated with mutant alleles of the CCR5 HIV-1 coreceptor, the molecular mechanism underlying resistance in repeatedly HIV-1-exposed, uninfected individuals (EU) is unclear. In this study, we performed complementary transcriptome and proteome analyses on peripheral blood T cells, and plasma or serum from EU, their HIV-1-infected sexual partners, and healthy controls, all expressing wild-type CCR5. We report that activated T cells from EU overproduce several proteins involved in the innate immunity response, principally those including high levels of peroxiredoxin II, a NK-enhancing factor possessing strong anti-HIV activity, and IL-22, a cytokine involved in the production of acute-phase proteins such as the acute-phase serum amyloid A (A-SAA). Cell supernatants and serum levels of these proteins were up-regulated in EU. Moreover, a specific biomarker for EU detected in plasma was identified as an 8.6-kDa A-SAA cleavage product. Incubation of in vitro-generated myeloid immature dendritic cells with A-SAA resulted in CCR5 phosphorylation, down-regulation of CCR5 expression, and strongly decreased susceptibility of these cells to in vitro infection with a primary HIV-1 isolate. Taken together, these results suggest new correlates of EU protection and identify a cascade involving IL-22 and the acute phase protein pathway that is associated with innate host resistance to HIV infection.

Acute-Phase Proteins↗
PubMed2006

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.

Adult↗
PubMed2006

Antiretroviral therapy-associated modulation of Th1 and Th2 immune responses in HIV-infected pregnant women.

A successful pregnancy is characterised by an increase in Th2 cytokines and suppression of Th1 cytokine production. A Th1 to Th2 cytokine shift is also observed in the disease progression of HIV infection. Highly active antiretroviral therapy (HAART) suppresses HIV viremia, increases CD4+ cell counts and counteracts the Th1 to Th2 shift. We hypothesised that the increased risk of premature delivery reported in HIV-infected, HAART-treated pregnant women is mediated through changes in the cytokine environment in pregnancy. Here, we present results relating to levels of interleukin (IL)-2 (Th1) and IL-10 (Th2) in peripheral blood mononuclear cells (PBMCs) measured three times during pregnancy in 49 HIV-infected women. Slope values representing the trend of repeated cytokine (IL-2-PHA, IL-2-Env, IL-10-PHA and IL-10-Env) measurements within women during pregnancy were estimated and median values compared by prematurity and HAART use. Multiple regression adjusted for HAART and cytokine slope clarified the additional and independent effect of HAART on prematurity risk. Results showed favourable immunomodulation induced by HAART with increased IL-2 and decreased IL-10. HAART use and IL-10-Env slopes were not significantly associated with prematurity risk, but each unit increase in IL-2-PHA slope was associated with an 8% increased risk of premature delivery (AOR, 1.08; 95% CI, 1.0-1.17; p=0.005). HAART use in pregnancy provides significant benefits in delaying HIV disease progression and reducing the risk of mother-to-child-transmission, but may be counterproductive in terms of successful pregnancy outcome.

Adult↗
PubMed2006

Immunogenicity and effect of a virosomal influenza vaccine on viral replication and T-cell activation in HIV-infected children receiving highly active antiretroviral therapy.

In order to evaluate the immunogenicity and the effect of a virosomal influenza vaccine on viral replication and T-cell activation in HIV-infected children receiving highly active antiretroviral therapy (HAART), 29 children infected with HIV-1 vertically (19 primed with a previous influenza vaccination and 10 who were not been immunized against influenza) were immunized with an intramuscular virosome-adjuvanted influenza vaccine. According to the European Agency for Evaluation of Medical Products (EMEA) criteria, the immunogenicity of the vaccine was adequate against all three influenza strains (A H1N1, A H3N2, and B) in the primed children, and against A H1N1 and A H3N2 in the unprimed children. After in vitro stimulation with vaccine antigens, the IFN-gamma levels in the peripheral blood mononuclear cells cultures increased significantly from a baseline level of 103.0 +/- 229.8 pg/ml to a 30-day level of 390.7 +/- 606.3 pg/ml (P < 0.05), with concentrations significantly higher (P < 0.05) in the primed children than in the unprimed children. No increase in plasma HIV-1 RNA or HIV-1 proviral DNA was observed in either subgroup, and the immunophenotype analyses demonstrated that the CD4+ cell counts and percentages, the CD4/CD8 ratio and activated lymphocytes remained stable in either group from baseline to 1 month after each vaccine dose. This study showed that the virosomal influenza vaccine does seem to be immunogenic in the majority of HIV-infected children receiving HAART and does not induce viral replication or T-cell activation. Given the possible influenza-related complications in children infected with HIV, these results support the use of this influenza vaccine in such patients.

Adolescent↗
PubMed2006

Failure to eradicate HIV despite fully successful HAART initiated in the first days of life.

Highly active antiretroviral therapy (HAART) started shortly after birth resulted in reversion of human immunodeficiency virus (HIV) plasma viremia, proviral DNA in PBMC, viral culture, and serum HIV antibodies to negative. Discontinuation of HAART 2 years after apparent HIV eradication, however, was followed by virus replication, CD4 decline, and destruction of HIV-specific lymphocytes, epitomizing the impossibility of HIV eradication.

Antiretroviral Therapy, Highly Active↗
PubMed2006

Hiv-specific secretory IgA in breast milk of HIV-positive mothers is not associated with protection against HIV transmission among breast-fed infants.

OBJECTIVES: To test whether secretory immunoglobulin A (sIgA) to human immunodeficiency virus (HIV) antigens in breast milk of HIV-positive women is associated with protection against HIV transmission among breast-fed infants. STUDY DESIGN: Nested, case-control design in which HIV-specific sIgA was measured in breast milk collected from 90 HIV-positive women enrolled in a study in Lusaka, Zambia. Milk samples were selected to include 26 HIV-positive mothers with infected infants (transmitters) and 64 mothers with uninfected infants (nontransmitters). RESULTS: HIV-specific sIgA was detected more often in breast milk of transmitting mothers (76.9%) than in breast milk of nontransmitting mothers (46.9%, P = .009). There were no significant associations between HIV-specific sIgA in breast milk and other maternal factors, including HIV RNA quantities in breast milk, CD4 count, and plasma RNA quantities. CONCLUSIONS: HIV-specific sIgA in breast milk does not appear to be a protective factor against HIV transmission among breast-fed infants.

Adult↗
PubMed2006

Synergy between mannose-binding lectin gene polymorphisms and supplementation with vitamin A influences susceptibility to HIV infection in infants born to HIV-positive mothers.

BACKGROUND: Mannose-binding lectin (MBL-2) allele variants are associated with deficiencies in innate immunity and have been found to be correlated with HIV infection in adults and children. OBJECTIVE: We tested whether MBL-2 variants among infants born to HIV-positive mothers have an increased susceptibility to HIV. DESIGN: MBL-2 allele variants were measured among 225 infants born to HIV-positive mothers enrolled in a trial in Durban, South Africa. Mothers of 108 infants were randomly assigned to receive vitamin A and beta-carotene supplementation and 117 to receive placebo. Infants were followed with regular HIV tests to determine rates of mother-to-child HIV transmission. RESULTS: A high proportion of infants were either homozygous (10.7%) or heterozygous (32.4%) for MBL-2 variants. MBL-2 variants within the placebo arm were associated with an increased risk of HIV transmission (odds ratio: 3.09; 95% CI: 1.21, 7.86); however, MBL-2 variants within the supplementation arm were not associated with an increased risk of transmission (P = 0.04; test of interaction). Among infants with MBL-2 variants, supplementation was associated with a decreased risk of HIV transmission (odds ratio: 0.37; 95% CI: 0.15, 0.91). CONCLUSION: We observed what appears to be a gene-environment interaction between MBL-2 variants and an intervention with vitamin A plus beta-carotene that is relevant to mother-to-child HIV transmission.

Adult↗
PubMed2005

Immunization with gp120-depleted whole killed HIV immunogen and a second-generation CpG DNA elicits strong HIV-specific responses in mice.

HIV-1 Immunogen is a gp120-depleted whole killed virus vaccine candidate formulated with Incomplete Freund's Adjuvant (HIV-IFA). We evaluated in a mouse model the immunogenicity of HIV-IFA by itself and when combined with HYB2055, an immunomodulatory oligonucleotide consisting of a novel DNA structure and synthetic CpR immunostimulatory motif, as an adjuvant. C57/BL6 mice were immunized with HIV-IFA alone or combined with HYB2055. Mice treated with HYB2055 or with PBS were used as controls. Compared to HIV-IFA alone, immunization with HIV-IFA and HYB2055 combination elicited strong production of HIV- and p24-specific IFNgamma, RANTES, MIP 1alpha, and MIP 1beta, as well as high titers of HIV- and p24-specific antibodies. Inclusion of HYB2055 also reduced levels of IL-5 produced by HIV-IFA alone. HYB2055 enhances the immunogenicity of HIV-IFA and shifts responses towards a type 1 cytokine profile. The immune enhancing effects of HYB2055 adjuvant were dose-dependent. These findings warrant clinical evaluation of the HIV-1 immunogen/HYB2055 candidate as a therapeutic vaccine for HIV-1 infected patients.

AIDS Vaccines↗
PubMed2005

Genotypes at chromosome 22q12-13 are associated with HIV-1-exposed but uninfected status in Italians.

OBJECTIVE: Despite multiple and repeated exposures to HIV-1, some individuals possess no detectable HIV genome and show T-cell memory responses to the viral antigens. HIV-1-reactive mucosal IgA detected in such uninfected individuals suggests their possible immune resistance against HIV. We tested if the above HIV-1-exposed but uninfected status was associated with genetic markers other than a homozygous deletion of the CCR5 gene. METHODS: Based on our mapping in chromosome 15 of a gene controlling the production of neutralizing antibodies in a mouse retrovirus infection, we genotyped 42 HIV-1-exposed but uninfected Italians at polymorphic loci in the syntenic segment of human chromosome 22, and compared them with 49 HIV-1-infected and 47 uninfected healthy control individuals by a closed testing procedure. RESULTS: A significant association was found between chromosome 22q12-13 genotypes and a putative dominant locus conferring anti-HIV-1 immune responses in the exposed but uninfected individuals. Distributions of linkage disequilibrium across chromosome 22 also differed between the exposed but uninfected and two other phenotypic groups. CONCLUSIONS: The data indicated the presence of a new genetic factor associated with the HIV-1-exposed but uninfected status.

Animals↗
PubMed2005

Alpha-defensins in the prevention of HIV transmission among breastfed infants.

Alpha-defensins have been observed to have anti-HIV activity but have not been investigated in relation to mother-to-child HIV transmission. We measured the concentration of alpha-defensins in breast milk of HIV-positive mothers and tested whether the concentrations were associated with HIV transmission. A nested case-control study of 32 HIV-positive women who transmitted HIV to their infants and 52 randomly selected HIV-positive women who did not transmit HIV to their infants was conducted in Lusaka, Zambia. alpha-Defensins were detected in most (79%) of the milk samples tested. Concentrations of alpha-defensins increased as breast milk HIV RNA quantity increased, and breast milk HIV RNA quantity was, in turn, a strong and significant predictor of HIV transmission. After adjustment for milk HIV RNA quantity, however, alpha-defensin concentration was significantly associated with a decreased risk of intrapartum and postnatal HIV transmission (odds ratio = 0.3, 95% confidence interval: 0.09-0.93). Our data suggest that there may be a role for alpha-defensins in prevention of HIV transmission to breastfed infants.

Adult↗
PubMed2005

Distinct patterns of HIV-specific memory T lymphocytes in HIV-exposed uninfected individuals and in HIV-infected patients.

BACKGROUND: Repeated exposure to HIV is not always associated with infection and multiple cohorts of HIV-exposed but seronegative individuals (ESN) have been described. HIV-specific CD4 and CD8 T lymphocytes are detected both in HIV patients and in ESN; we verified whether different patterns of HIV-specific memory T lymphocytes would be detected in individuals in whom exposure to HIV results or does not result in infection. METHODS: Gag-specific T cells were analysed in 15 ESN, 14 HIV patients, and 15 healthy controls using extensive flow cytometry analysis. RESULTS: Data confirmed that gag-specific T lymphocytes are present in ESN. Gag-specific T cells mainly secrete interleukin-2 in ESN and interferon-gamma in HIV patients. In addition the CD4/CD8 and the memory/naive ratios are altered, central memory (45RA-/CCR7+) CD4 and CD8 T lymphocytes are more abundant, and terminally differentiated (45RA+/CCR7- and 27-/28-) CD8 T lymphocytes are augmented in ESN individuals. CONCLUSIONS: Exposure to HIV occurs in high risk seronegative individuals; the observation that naive cells and CM are skewed in ESN indicate that this exposure is robust enough to modulate the CM/EM ratio. The increase in late effectors and in natural killer cells seen in ESN suggests a role for these cells in preventing actual infection.

Adult↗
PubMed2005

Programmed cell death of myelin basic protein-specific T lymphocytes is reduced in patients with acute multiple sclerosis.

We investigated the apoptosis of myelin basic protein (MBP)-specific T lymphocytes in multiple sclerosis (MS) patients with acute (AMS) or stable (SMS) MS by evaluating the expression of apoptosis markers on peripheral cells. Cells of healthy controls (HC) were evaluated as well. Results showed that mitogen-stimulated apoptosis was comparable among patients and controls, whereas MBP-stimulated CD4+ and CD8+ 7-AAD+ and 7-AAD+ Fas+ cell (apoptotic cells) were significantly reduced in AMS patients. A reduction of the apoptotic rate of myelin-specific CD4+ and CD8+ T lymphocytes could be involved in the immune-mediated destruction of the myelin sheath seen in AMS patients.

Acute Disease↗
PubMed2004

Human alpha defensin in HIV-exposed but uninfected individuals.

Human alpha defensins 1, 2, and 3 are produced by CD8 T cells of HIV-infected long-term nonprogressors and have an antiviral activity. alpha Defensins were examined in peripheral blood mononuclear cells (PBMCs), cervical-vaginal mononuclear cells (CVMCs), and cervical biopsies of 9 HIV-1-exposed but uninfected women (ESNs), 10 HIV-infected patients (HIV), and 13 low-risk healthy controls (HCs). Results showed that, whereas alpha defensin production and alpha defensin-expressing CD8 lymphocytes were comparable in ESNs and HIV patients, constitutive alpha defensin production by peripheral CD8 and CVMCs was augmented in ESNs compared with HCs (P = 0.001 and P = 0.058, respectively); alpha defensin mRNA was increased in PBMCs of ESNs; unstimulated, alpha defensin-expressing peripheral and mucosal CD8 lymphocytes were 10-fold higher in ESNs compared with HCs (P = 0.003 and P = 0.01, respectively); and alpha defensin mRNA and alpha defensin-expressing cells were augmented in cervical biopsies of ESN compared with HCs (mRNA:P = 0.03). The differences were reduced upon in vitro mitogen stimulation. A robust constitutive production of alpha defensin is seen in HIV-exposed uninfected individuals; these peptides could have a role in the potentially protective immune response that characterizes ESNs.

Biopsy↗
PubMed2004

Granule-dependent mechanisms of lysis are defective in CD8 T cells of HIV-infected, antiretroviral therapy-treated individuals.

BACKGROUND: HIV-specific cytotoxic T-cell (CTL) responses are defective in HIV-infected patients undergoing antiretroviral therapy (ART). This defect has been attributed to the decreased antigenic burden secondary to ART-associated suppression of HIV-replication, and is responsible for the rebounds of viraemia that occur when patients interrupt therapy. CTL are stimulated by type 1 cytokines and can kill targets via granule-dependent (perforin and granzymes) and -independent (tumour necrosis factor-alpha, CD95) mechanisms. METHODS: Granule-dependent and granule-independent mechanisms of CTL killing, as well as type 1 cytokine production by CD4 T cells, were analysed in 57 chronically HIV-infected ART-treated or ART-untreated individuals. RESULTS: The results can be summarized as follows: the frequency of gp160 (env)-specific interferon-gamma-secreting CD8 T lymphocytes correlates positively with HIV viraemia in ART-treated and -untreated patients; Env-specific perforin- and granzymes-expressing CD8 T lymphocytes, and Env-stimulated perforin and granzymes mRNA, are reduced in ART-treated patients independently of HIV viral load and of type 1 cytokine production; tumour necrosis factor-alpha production is increased in ART-treated individuals; and Env-specific immature CD8+28+27+ cells are only marginally augmented in ART-treated patients, Similar results are observed in cytomegalovirus-specific CD8 T cells and peripheral blood mononuclear cells. CONCLUSIONS: A defect of CTL function that selectively affects the granule-dependent mechanisms of lysis is observed in ART-treated individuals. Because interferon-gamma production is higher in these patients, this could be a defect primarily involving CTL. These data suggest an independence of CD8 T-cell numbers and their lytic ability in HIV-infected, ART-receiving patients. Immunomodulants are needed to successfully treat HIV infection.

Adult↗
PubMed2004

Growth hormone in T-lymphocyte thymic and postthymic development: a study in HIV-infected children.

OBJECTIVES: Growth hormone (GH) plays a role in thymic function, and recombinant GH may stimulate thymopoiesis in HIV-infected individuals. We performed immunologic analyses in 26 antiretroviral-treated children matched for age, pubertal status, clinical parameters, and antiretroviral exposure who did or did not show an impaired response to GH-release stimulation tests with arginine + GH-releasing hormone. RESULTS: The following abnormalities were found in GH-deficient compared with GH-nondeficient children after >4 years of therapy: CD4 count ( P = .02) and percentage ( P = .03), CD4 as percentage of normal cells for age ( P = .003), serum interleukin-7 concentration ( P = .02), and thymic volume ( P = .01). Naive CD4 (4+62+RA+ and 4+CCR7+RA+) and CD8 (8+CCR7+RA+) lymphocytes were lower in GH-deficient children ( P = .003; P = .007; and P = .02, respectively). Postthymic pathways were also impaired in GH-deficient children. Thus, central memory (4+CCR7+RA-) CD4+ cells were reduced ( P = .006), whereas effector memory (4+CCR7-RA-) CD4+ cells ( P = .002) and late effector CD8+ lymphocytes (8+CCR7-RA+ and 8+27-28-) ( P = .009 and P = .002, respectively) were increased in these children. CONCLUSIONS: Growth hormone plays a role in thymic and postthymic pathways, and defective GH production may be associated with incomplete immunoreconstitution. Immunomodulant agents (including GH) could be useful in patients with defective GH production.

Adolescent↗
PubMed2004

Interleukin-10 and interleukin-6 gene polymorphisms as risk factors for Alzheimer's disease.

In the pathogenesis of Alzheimer disease (AD), it has been proposed that the anti-inflammatory interleukins such as IL-10 regulate beta-amyloid-induced microglial inflammatory responses inhibiting the proinflammatory cytokine IL-6. Since the promoters of the IL-10 and IL-6 genes show single nucleotide polymorphisms (SNPs) (IL-10: -1082 G --> A; IL-6: -174 G --> C), we investigated these SNPs and cytokine production by peripheral blood mononuclear cells in 65 AD patients and 65 controls (HC). In AD there was a significant increase of the -1082A IL-10 allele (P=0.009) and a decrease of -1082GG genotype (P=0.019). The frequency of the GG IL-6 genotype in AD was lower and the C allele significantly higher (P <0.005). The co-occurrence of IL-10 A and IL-6 C alleles significantly raised the odds ratio (OR 11.2, confidence interval: CI 1.3-97.3; P <0.05) independently of apolipoprotein E4 (adjusted OR 10.3, CI 1-108; P <0.05). Only amyloid-stimulated IL-10 production differed between the groups (P=0.023). These results raise questions regarding the inflammatory theory in AD, pointing to a pivotal role of IL-10 and IL-6 and a selective alteration in this network.

Aged↗