JEFFERSON RUSSO VICTOR

(Fonte: Lattes)
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Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina

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  • article 8 Citação(ões) na Scopus
    Maternal immunization downregulates offspring TCD4 regulatory cells (Tregs) thymic maturation without implications for allergy inhibition
    (2018) OLIVEIRA, Marilia Garcia de; LIRA, Aline Aparecida de Lima; SGNOTTO, Fabio da Ressureicao; INOUE, Amanda Harumi Sabo; BELTRAME, Giovanna Rossi; SILVA, Debora da; MENGHINI, Ricardo Palamar; DUARTE, Alberto Jose da Silva; VICTOR, Jefferson Russo
    The regulation of offspring allergy development mediated by maternal immunization was evidenced by several groups, and this mechanism seems to involve the induction of regulatory T cells (Tregs) on offspring. Here, we aimed to evaluate whether the effect of maternal immunization on offspring Tregs occurs as a result of peripheral or central modulation. Briefly, C57BL/6 female mice were immunized with OVA in Alum or Alum alone and boosted with OVA in saline or saline only after 10 and 20 days. Non-immunized offspring serum, thymus and spleen were evaluated at 3 or 20 days old, and some groups of pups were submitted to neonatal OVA-immunization protocol for the subsequent evaluation of antibody production and allergic response. Our experimental protocol could be validated because maternal OVA-immunization inhibited offspring allergic response as evidenced by the suppression of offspring IgE production and allergic lung inflammation. Interestingly, maternal immunization reduced the frequency of offspring thymic Tregs with an opposite effect on spleen Tregs. Furthermore, after neonatal immunization, the frequency of lung-infiltrated Tregs was also augmented on offspring from immunized mothers. In conclusion, maternal OVA-immunization can inhibit the thymic maturation of offspring Tregs without implications on peripheral Tregs induction and allergy inhibition.
  • article 15 Citação(ões) na Scopus
    Tolerogenic microenvironment in neonatal period induced by maternal immunization with ovalbumin
    (2014) MUNIZ, Bruno Pacola; VICTOR, Jefferson Russo; OLIVEIRA, Luana de Mendonca; LIRA, Aline Aparecida de Lima; PERINI, Adenir; OLIVO, Clarice Rosa; ARANTES-COSTA, Fernanda Magalhaes; MARTINS, Milton Arruda; DUARTE, Alberto Jose da Silva; SATO, Maria Notomi
    Maternal immunization with allergens, such as ovalbumin (OVA), can inhibit the development of an allergic response in offspring. The regulatory mechanisms seem to be mediated by maternal antibodies (MatAbs) and factors generated by the maternal fetal interface. The aim of this study was to verify the pathways of inhibitory Ab transference after maternal immunization with OVA and the effect of the offspring's dendritic cells (DCs) on the generation of regulatory T (Treg) cells. We verified that preconceptional OVA immunization induces high levels of proinflammatory and regulatory cytokines in the amniotic fluid, allowing the transference of high levels of anti-OVA IgG1 Abs to the offspring. Using an adoptive nursing protocol, we verified that maternal immunization leads to MatAb transference by the placental route and by breastfeeding contribute to the inhibition of anaphylactic IgE and IgG1 Ab responses in immunized offspring. We observed that maternal immunization decreased eosinophil numbers in recovered bronchoalveolar lavage fluid and in the lung tissue, whereas with a lack of control of airway responsiveness to methacholine. Maternal immunization induced in young offspring a decreased percentage of CD11c+ DCs expressing MHC class II and CD40 molecules. Moreover, DCs from both groups of offspring when pulsed with OVA, were able to induce Treg cells in vitro. Similarly, OVA immunization at the neonatal stage increased the frequency of Treg cells, regardless of the mother's immunization status. These findings emphasize that maternal immunization leads to a complex interaction of regulatory factors, with MatAbs, DCs and Treg cells affecting the tolerance of offspring during an allergic response.
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    IgG from atopic dermatitis patients induces IL-17 and IL-10 production in infant intra-thymic TCD4 and TCD8 cells
    (2018) SGNOTTO, F. R.; OLIVEIRA, M. G.; LIRA, A. A. L.; INOUE, A. H. S.; TITZ, T. O.; ORFALI, R. L.; BENTO-DE-SOUZA, L.; SATO, M. N.; AOKI, V.; DUARTE, A. J. S.; VICTOR, J. R.
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  • article 13 Citação(ões) na Scopus
    Preconceptional allergen immunization can induce offspring IL-17 secreting B cells (B17): do they share similarities with regulatory B10 cells?
    (2018) LIRA, Aline Aparecida de Lima; DE-OLIVEIRA, Marilia Garcia; INOUE, Amanda Harumi Sabo; BELTRAME, Giovanna Rossi; DUARTE, Alberto Jose da Silva; VICTOR, Jefferson Russo
    Background: IL-17-producing B cells can be identified in both mice and human and were named B17 cells. The role of B17 cells still needs to be elucidated and its inflammatory or regulatory functions remain controversial. Objective: We evaluate the effect of maternal immunization with OVA on offspring B cells that produces IL-17 and can show a regulatory potential by IL-10 production. Methods: C57BL/6 WT, IL-10(-/-) or CD28(-/-) female mice were immunized or not with OVA in Alum, and immunized females were boosted after 10 and 20 days. Immunized and non immunized females were mated, and pups from both groups were evaluated at 3 or 20 days old (d.o.). Some offspring from the aforementioned two groups were immunized with OVA at 3 d.o., boosted after 10 days and evaluated at 20 d.o. Results: Maternal immunization with OVA induced offspring B cells to produce IL-17 at higher intensity compared to the control group of offspring at 3 d.o. This effect was maintained until 20 d.o. and even after neonatal immunization with OVA. The co-production of IL-10 on offspring IL-17 + B cells is up-regulated in response to maternal immunization with OVA. Maternal immunization with OVA on IL-10(-/-)mice reveals reduced percentage and mean of fluorescence intensity of IL-17 on B cells of offspring. Conclusion: Preconception OVA immunization can induce offspring B cells that produce IL-17 at higher intensity and co-produce mainly IL-10. This could be the reason why B17 cells had been described in the literature with controversial roles upon their regulatory function.
  • article 4 Citação(ões) na Scopus
    Preconception immunization can modulate intracellular Th2 cytokine profile in offspring: in vivo influence of interleukin 10 and B/T cell collaboration
    (2018) OLIVEIRA, Marilia Garcia de; LIRA, Aline Aparecida de Lima; SGNOTTO, Fabio Da Ressureicao; INOUE, Amanda Harumi Sabo; DUARTE, Alberto Jose da Silva; VICTOR, Jefferson Russo
    Introduction: In the last few years our group has been studying the mechanisms involved in the inhibition of allergy in offspring mediated by preconception maternal immunization, but these mechanisms are not fully understood. Such mechanisms that we have studied aimed at the passive transfer of maternal antibodies and its influence on offspring immune status. Aim of the study: To evaluate whether maternal immunization could modulate intracellular Thl/ Th2 profiles in offspring. Material and methods: C57BL/6 female wild type mice (WT), interleukin (IL)-10(-/-)or CD28(-/-) mice were immunized or not with ovalbumin (OVA) and were mated with respective lineage males and offspring were evaluated at 3 days old (d.o.), 20 d.o., or 20 d.o. after neonatal immunization. Results: Preconception OVA immunization induced a marked reduction in IL-4 secretion by TCD4+ cells of WT offspring when compared with offspring from non-immunized mothers. The maternal immunization of IL-10(-/- )mice induced an increase in the TCD4+IL-4+ percentage in offspring and a reduction in TCD4+IFN-gamma+ cells. The maternal immunization in CD28(-/-) mice induced augment IL-4 intensity in 3 and 20 d.o. offspring TCD4+ cells. Conclusions: Our results reveal that maternal immunization with OVA can down-regulate the Th2 pattern in offspring and this regulation is dependent on IL-10 and B/T cell collaboration.
  • article 21 Citação(ões) na Scopus
    Low doses of IgG from atopic individuals can modulate in vitro IFN-gamma production by human intra-thymic TCD4 and TCD8 cells: An IVIg comparative approach
    (2017) SGNOTTO, Fabio da Ressureicao; OLIVEIRA, Marilia Garcia de; LIRA, Aline Aparecida de Lima; BENTO-DE-SOUZA, Luciana; DUARTE, Alberto Jose da Silva; VICTOR, Jefferson Russo
    The regulatory effect of allergic responses induced by IgG antibodies on human intra-thymic cells has not been reported in the literature. The aim of this study was to evaluate the possible differential effect of purified IgG from atopic and non-atopic individuals on human intra-thymic T cell cytokine production. Thymic tissues were obtained from 14 patients who were less than 7 d old. Additionally, blood samples were collected from atopic and non-atopic volunteers. Thymocytes and peripheral blood mononuclear cells were cultured with purified atopic or non-atopic IgG, and intracellular cytokine production was assessed. Purified IgG did not influence the frequency or viability of human intra-thymic T cells. Purified non-atopic IgG induced greater IFN-gamma production by intra-thymic CD4+CD8+ T cells than did the mock treatment and atopic IgG. A similar effect of purified non-atopic IgG on TCD8 cells was observed compared with the mock treatment. Atopic IgG inhibited IFN-gamma and TGF-beta production by intra-thymic TCD4 cells. Treatment with intravenous immunoglobulin resulted in intermediate levels of IFN-gamma and TGF-beta in intra-thymic TCD4 cells compared with treatment with atopic and non-atopic IgG. Peripheral TCD4 cells from non-atopic individuals produced IFN-gamma only in response to atopic IgG. This report describes novel evidence revealing that IgG from atopic individuals may influence intracellular IFN-gamma production by intra-thymic T cells in a manner that may favor allergy development.
  • article 19 Citação(ões) na Scopus
    Preconception allergen sensitization can induce B10 cells in offspring: a potential main role for maternal IgG
    (2017) OLIVEIRA, Marlia Garcia de; OLIVEIRA, Luana de Mendonca; LIRA, Aline Aparecida de Lima; SGNOTTO, Fabio da Ressureicao; DUARTE, Alberto Jose da Silva; SATO, Maria Notomi; VICTOR, Jefferson Russo
    Background: The mechanisms through which allergies can be inhibited after preconception immunization with allergens are not fully understood. We aimed to evaluate whether maternal immunization can induce a regulatory B (B10) cell population in offspring in concert with allergy inhibition. Methods: C57BL/6 females were or were not immunized with OVA and were mated with normal WT males. Their offspring were evaluated at 3 days of age or 20 days after neonatal immunization. Human peripheral B cells from atopic and non-atopic individuals were also evaluated. Results: Preconception OVA immunization induced B10 cells in offspring, and IL-10 production appeared to be critical for FcyRIIB upregulation in offspring B cells. Murine and human IL-10-producing B cells responded in vitro to IgG according to the atopic repertoire of the cells. Conclusions: Our results reveal that maternal immunization induces allergen-specific B10 cells in offspring and a pivotal role for the IgG repertoire in IL-10 production by murine and human B cells.
  • article 16 Citação(ões) na Scopus
    Maternal IgG impairs the maturation of offspring intrathymic IL-17-producing gamma delta T cells: Implications for murine and human allergies
    (2019) DE-OLIVEIRA, Marilia G.; LIRA, Aline A. L.; SGNOTTO, Fabio R.; INOUE, Amanda H. S.; SANTOS, Ludimila S.; NAKAMATSU, Bernardo Y.; DUARTE, Alberto J. S.; LEITE-DE-MORAES, Maria; VICTOR, Jefferson R.
    Background The precise mechanism involved in the acquisition of the IL-17+ profile of gamma delta T cells, the ligands responsible for this change, and whether this default is acquired during intrathymic maturation need to be elucidated. Objective This study aimed to evaluate whether IL-17-producing gamma delta T cells are present in the airways of tolerant offspring from allergen-sensitized mothers and the possible implication of maternal IgG in the generation of these cells. Methods Female mice were immunized or not, and the allergic response, frequency of gamma delta T cell subsets and cytokine production of the offspring were analysed by flow cytometry. The effects of passive in vivo transfer of purified IgG were investigated in offspring. A translational approach was employed to analyse gamma delta T cells in the thymus and PBMCs from humans. Results Maternal immunization reduced the frequency of spontaneous IL-17-producing gamma delta T cells in the thymus, spleen and lung of offspring. This effect was mimicked by the in vivo treatment of females with purified IgG. IgG directly interacted with gamma delta T cell membranes. The modulatory effect of human IgG on human infant intrathymic and adult peripheral gamma delta T cells showed similarities to murine gamma delta T cells, which is rarely reported in the literature. Conclusions & Clinical Relevance Together, our results reveal that IgG from potentially tolerant atopic mothers can influence offspring thymic IL-17-producing gamma delta T cell maturation. Furthermore, we suggest that IgG is an unprecedented modulatory factor of murine and human gamma delta T cells. These observations may support the future development of IgG-based immunoregulatory therapeutic strategies.
  • article 21 Citação(ões) na Scopus
    IgG from atopic dermatitis patients induces IL-17 and IL-10 production in infant intrathymic TCD4 and TCD8 cells
    (2018) SGNOTTO, Fabio D. R.; OLIVEIRA, Marilia G. de; LIRA, Aline A. L.; INOUE, Amanda H. S.; TITZ, Tiago O.; ORFALI, Raquel L.; BENTO-DE-SOUZA, Luciana; SATO, Maria N.; AOKI, Valeria; DUARTE, Alberto J. S.; VICTOR, Jefferson R.
    IntroductionOur group recently demonstrated that IgG modulates T cell cytokine production during the maturation process in the human thymus. The effects of this modulation are IgG repertoire dependent and can exert a systemic and long-term impact. ObjectiveTo investigate whether IgG from atopic dermatitis (AD) patients can modulate cytokine production of infant intrathymic TCD4 and TCD8 cells in vitro. MethodsThymic tissues were obtained from newborn children from nonatopic mothers, and thymocytes were cultured for 6 days with purified IgG from AD patients or with intravenous immunoglobulin (IVIG) or mock conditions as controls. Cells were gated as double positive T cells (TDP(-)CD4(+)CD8(+)), TCD4 cells (CD4(+)CD8(-)), or TCD8 cells (CD4(-)CD8(+)), and intracellular levels of IL-17A, IFN-, TNF-, IL-4, IL-10, and TGF- were evaluated by flow cytometry. ResultsCompared to mock and IVIG culture conditions, IgG of AD individuals induced in vitro intracellular production of IL-17 and IL-10 by intrathymic TDP, TCD4, and TCD8 cells of infants. TGF- was also detected at a higher frequency in response to AD IgG in TDP and TCD8 cells compared to mock and IVIG cultured conditions. An opposite effect was detected upon IFN- production in TCD4 cells, such that AD IgG reduced IFN- production compared to production under mock conditions but not under IVIG conditions. ConclusionIgG of AD patients can stimulate cytokine production in infant thymocytes and thus resembles the peripheral profile observed in adults. These findings suggest a novel mechanism that can contribute to AD pathogenesis.