JEFFERSON RUSSO VICTOR
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
28 resultados
Resultados de Busca
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- IgG from atopic individuals can mediate non-atopic infant thymic and adult peripheral CD8(+) TC2 skewing without influence on TC17 or TC22 cells(2021) SOUSA, T. R. de; SGNOTTO, F. Da Ressureicao; FAGUNDES, B. Oliveira; SANTOS, L. Souza; DUARTE, A. J. Da Silva; VICTOR, J. R.The potential of IgG antibodies as allergy regulators has been discussed for decades and was brought to light that anti-allergen IgG is related to allergy inhibition in children during the first years of life and that IgG repertoire can differ between atopic and non-atopic individuals. Here, we aimed to evaluate in vitro the differential effects of purified IgG from atopic and non-atopic individuals on the production of IL-4, IL-17, and IL-22 by human intra-thymic and mature peripheral CD8(+) T cells respectively termed as TC2, TC17, and TC22 cells. We additionally evaluated the IFN-gamma production by CD8(+) T cells. Thereupon we used infants thymic tissues from non-atopic mothers and blood samples from individuals clinically classified as non-atopic. Thymocytes or PBMCs were cultured with IgG from atopic or non-atopic individuals. As controls, we used commercial IgG (Intravenous immunoglobulin IVIg) or mock condition. The phenotype and intracellular cytokine production were evaluated using flow cytometry. IgG from atopic individuals could increase the frequency of TC2 cells in non-atopic infant thymic and adult peripheral cell cultures compared to all control conditions. Due to the TC2 cell's potential to collaborate with pathology and severity of asthma in humans, this evidence can cooperate with the understanding of the development of an atopic state.
- IgG from Adult Atopic Dermatitis (AD) Patients Induces Nonatopic Neonatal Thymic Gamma-Delta T Cells (gamma delta T) to Acquire IL-22/IL-17 Secretion Profile with Skin-Homing Properties and Epigenetic Implications Mediated by miRNA(2022) FAGUNDES, Beatriz Oliveira; SOUSA, Thamires Rodrigues de; NASCIMENTO, Andrezza; FERNANDES, Lorena Abreu; SGNOTTO, Fabio da Ressureicao; ORFALI, Raquel Leao; AOKI, Valeria; DUARTE, Alberto Jose da Silva; SANABANI, Sabri Saeed; VICTOR, Jefferson Russogamma delta T cells mature in the human thymus, and mainly produce IL-17A or IFN-gamma, but can also produce IL-22 and modulate a variety of immune responses. Here, we aimed to evaluate whether IgG from AD patients (AD IgG) can functionally modulate thymic nonatopic gamma delta T cells. Thymic tissues were obtained from 12 infants who had not had an atopic history. Thymocytes were cultured in mock condition, or in the presence of either AD IgG or therapeutic intravenous IgG (IVIg). Following these treatments, intracellular cytokine production, phenotype, and microRNA expression profiles were investigated. AD IgG could downregulate alpha 4 beta 7, upregulate CLA, and induce the production of IFN-gamma, IL-17, and IL-22 in gamma delta T cells. Although both AD IgG and IVIg could directly interact with gamma delta T cell membranes, AD IgG could reduce gamma delta T cell apoptosis. AD IgG could upregulate nine miRNAs compared to IVIg, and six when compared to the mock condition. In parallel, some miRNAs were downregulated. Target gene prediction and functional analysis indicated that some target genes were enriched in the negative regulation of cellular transcription. This study shows that AD IgG influences the production of IL-17 and IL-22 by intrathymic nonatopic gamma delta T cells, and demonstrates epigenetic implications mediated by miRNAs.
- The Potential of IgG to Induce Murine and Human Thymic Maturation of IL-10+B Cells (B10) Revealed in a Pilot Study(2020) INOUE, Amanda Harumi Sabo; LIRA, Aline Aparecida de Lima; DE-OLIVEIRA, Marilia Garcia; SOUSA, Thamires Rodrigues de; SGNOTTO, Fabio da Ressureicao; DUARTE, Alberto Jose da Silva; VICTOR, Jefferson RussoRegulatory B (B10) cells can control several inflammatory diseases, including allergies; however, the origin of peripheral B10 cells is not fully understood, and the involvement of primary lymphoid organs (PLOs) as a primary site of maturation is not known. Here, using a murine model of allergy inhibition mediated by maternal immunization with ovalbumin (OVA), we aimed to evaluate whether B10 cells can mature in the thymus and whether IgG can mediate this process. Female mice were immunized with OVA, and offspring thymus, bone marrow, spleen, lung, and serum samples were evaluated at different times and after passive transfer of purified IgG or thymocytes. A translational approach was implemented using human nonatopic thymus samples, nonatopic peripheral blood mononuclear cells (PBMCs), and IgG from atopic or nonatopic individuals. Based on the expression of CD1d on B cells during maturation stages, we suggest that B10 cells can also mature in the murine thymus. Murine thymic B10 cells can be induced in vitro and in vivo by IgG and be detected in the spleen and lungs in response to an allergen challenge. Like IgG from atopic individuals, human IgG from nonatopic individuals can induce B10 cells in the infant thymus and adult PBMCs. Our observations suggest that B10 cells may mature in the thymus and that this mechanism may be mediated by IgG in both humans and mice. These observations may support the future development of IgG-based immunoregulatory therapeutic strategies.
- Gamma-delta (gamma delta) T cell-derived cytokines (IL-4, IL-17, IFN-gamma and IL-10) and their possible implications for atopic dermatitis development(2023) FAGUNDES, Beatriz Oliveira; DE-SOUSA, Thamires Rodrigues; VICTOR, Jefferson RussoAtopic dermatitis (AD) is a chronic disease related to skin disorders that affect individuals in their childhood and can persist or start in adulthood. Patients affected by this disease commonly show skin lesions on the body surface (mainly on the upper and lower limbs) and allergic rhinitis or asthma crises. Looking at the disease from a molecular perspective, the major cytokines involved in inflammatory skin diseases, not only AD, include IL-4, IL-17, IFN-gamma and IL-10. Although they can produce these cytokines and infiltrate the affected epithelia in patients with AD, gamma delta T cells are still almost unexplored. In this update, we briefly discuss the involvement of IL-4, IL-17, IFN-gamma and IL-10 in the pathophysiology of AD and the possible role of gamma delta T cells during the inflammatory process.
- 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 RussoThe 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.
- IgG from atopic dermatitis patients induces non-atopic infant thymic invariant natural killer T (iNKT) cells to produce IL-4, IL-17, and IL-10(2020) SANTOS, Ludimila S.; SGNOTTO, Fabio da Ressureicao; SOUSA, Thamires R.; ORFALI, Raquel L.; AOKI, Valeria; DUARTE, Alberto Jose da Silva; VICTOR, Jefferson R.Background Atopic dermatitis (AD) pathogenesis still needs to be elucidated, but invariant natural killer T (iNKT) cell involvement was already described by several groups. Our group has demonstrated that IgG antibodies purified from AD patients can modulate cytokine production by thymic T cells. Here we aimed to investigate if IgG from AD patients can modulate infant non-atopic thymic iNKT cells cytokine production in order to collaborate with the elucidation of AD development in infancy. Methods Thymic tissues were obtained from children from non-atopic mothers, and IgG was purified from AD patients diagnosed as moderate or severe and, as controls, from subjects clinically classified as non-atopic individuals. PBMCs from non-atopic individuals were also used in this study. Results Our results demonstrated that IgG from AD patients could induce non-atopic children thymic iNKT cells to produce higher levels of intracellular IL-4, IL-10, and IL-17 when compared to all control conditions. No effect was observed in non-atopic adults peripheral iNKT. We also observed that IgG from AD patients induces an increase in the expression of CD4 and Ror gamma t transcription factor in non-atopic children thymic iNKT cells compared to the condition of all controls. Conclusions These observations suggest that IgG from AD patients can induce a cytokine profile by thymic iNKT cells from non-atopic infants compatible with the observations in AD development, which can collaborate with the elucidation of AD pathogenesis.
- 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 NotomiMaternal 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.
- Differential modulation of IL-4, IL-10, IL-17, and IFN-? production mediated by IgG from Human T-lymphotropic virus-1 (HTLV-1) infected patients on healthy peripheral T (CD4+, CD8+, and ?d) and B cells(2023) MACHADO, Nicolle Rakanidis; FAGUNDES, Beatriz Oliveira; FERNANDES, Lorena Abreu; OLIVEIRA, Augusto Cesar Penalva de; NUKUI, Youko; CASSEB, Jorge; CUNHA, Fernando Roberto Machado; NALI, Luiz Henrique da Silva; SANABANI, Sabri Saeed; VICTOR, Jefferson RussoHuman T-lymphotropic virus 1 (HTLV-1) infected individuals remain as asymptomatic carriers (ACs) or can develop the chronic neurological disorder HTLV-1-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP) or the adult T-cell leukemia/lymphoma (ATLL), and the immunological mechanisms involved in this pathologies need to be elucidated. Recently, it has been demonstrated that induced or naturally developed IgG repertoires obtained from different groups of donors, grouped by immune status, can modulate human T and B cell functions. Here we aimed to evaluate if the IgG obtained from HTLV-1-infected ACs, HAM/TSP, and ATLL patients can differentially modulate the production of cytokines by human T and B cells. With this purpose, we cultured PBMCs with IgG purified from ACs, HAM/TSP, or ATLL donors and evaluated the frequency and intracellular cytokine production by flow cytometry. Our results indicate that IgG from HAM/TSP patients could induce an augment of IL-17-producing CD4+ T cells, reduce the frequency of IL-4-producing CD4+ T cells, increase IFN-?-producing CD8+ T cells, and reduce IL-4-producing CD8+ T cells. IgG from ATLL could reduce the frequency of IL-4-producing CD4+ T cells, similarly to IgG from HAM/TSP /TSP, and could reduce the frequency of IFN-?-producing ?dT cells without influence on IL-17- and IL4-producing ?dT and could reduce the frequency of IL-10- producing B cells. Finally, IgG from both HAM/TSP and ATLL patients could reduce the frequency of IFN-? producing B cells. In conclusion, these results suggest that these preparations are active, partly overlapping in their effects, and able to elicit distinct effects on target populations.
- IgG from Non-atopic Individuals Induces In Vitro IFN-gamma and IL-10 Production by Human Intra-thymic gamma delta T Cells: A Comparison with Atopic IgG and IVIg(2019) SANTOS, Ludimila Souza; SGNOTTO, Fabio da Ressureicao; INOUE, Amanda Harumi Sabo; PADRECA, Archangelo Fernandes; MENGHINI, Ricardo Palamar; DUARTE, Alberto Jose da Silva; VICTOR, Jefferson RussoMatured in the thymus, gamma delta T cells can modulate the development of allergy in humans. The main gamma delta T cell subsets have been described as interleukin (IL)-17A or interferon (IFN)-gamma producers, but these cells can also produce other modulatory cytokines, such as IL-4 and IL-10. Here, we aimed to evaluate whether IgG can modulate the profile of cytokine production by gamma delta T cells during their maturation in the thymus and after its migration to peripheral tissues. Thymic tissues were obtained from 12 infants, and peripheral blood mononuclear cells (PBMCs) were obtained from adults (both groups without an atopic background). IgG was purified from atopic and non-atopic volunteers. Thymocytes and PBMCs were cultured with purified atopic or non-atopic IgG, and intracellular cytokine production and phenotype were assessed. Mock and IVIg conditions were used as controls. IgG from non-atopic individuals induced IFN-gamma and IL-10 production by thymic gamma delta T cells, and no effect was observed on peripheral gamma delta T cells. IL-17 production was inhibited by non-atopic IgG on thymic gamma delta T cells and augmented by atopic IgG on peripheral gamma delta T cells. Modulated thymic gamma delta T cells did not produce IFN-gamma and IL-10 simultaneously. We additionally evaluated the phenotype of intrathymic gamma delta T cells and observed that IgG from all groups could induce CD25 expression and could not influence the CD28 expression of these cells. This report describes evidence revealing that IgG may influence the production of IFN-gamma and IL-10 by intrathymic gamma delta T cells depending on the donor atopic state. This observation is unprecedented and needs to be considered in further studies in the IgG immunotherapy field.
- Natural Self-Ligand Gamma Delta T Cell Receptors (gamma delta TCRs) Insight: The Potential of Induced IgG(2020) SOUSA, Thamires Rodrigues de; VICTOR, Jefferson RussoA gamma delta T cell acquires functional properties in response to the gamma delta T cell receptor gamma delta TCR signal strength during its development in the thymus. The elucidation of the potential ligands of gamma delta T cell receptors are of extreme importance; however, they are still not understood. Here we revise the actual state of the art of candidates to exert the function of gamma delta TCR ligands, and propose a theoretical contribution about new potential ligands of gamma delta TCRs, based on biological and hypothetical pieces of evidence in the literature. In conclusion, we hypothetically suggest a possible role of induced antibodies according to the individual's immune status, mainly of the IgG subclass, acting as gamma delta TCR ligands. Considering that IgG production is involved in some essential immunotherapy protocols, and almost all vaccination protocols, our discussion opens a new and broad field to further exploration.
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