36 results on '"Arruvito L"'
Search Results
2. IL-6 trans-signaling and the frequency of CD4+FOXP3+ cells in women with reproductive failure
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Arruvito, L., Billordo, A., Capucchio, M., Prada, M.E., and Fainboim, L.
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- 2009
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3. Limited expansion and functionality of inducible regulatory T cells in women with recurrent spontaneous abortions: L-15
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Arruvito, L, Sotelo, A I, Billordo, A, and Fainboim, L
- Published
- 2009
4. KIR genes polymorphism in Argentinean Caucasoid and Amerindian populations
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Flores, A. C., Marcos, C. Y., Paladino, N., Capucchio, M., Theiler, G., Arruvito, L., Pardo, R., Habegger, A., Williams, F., Middleton, D., and Fainboim, L.
- Published
- 2007
5. Increased frequencies of activating natural killer receptors are associated with liver injury in individuals who do not eliminate hepatitis C virus
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Paladino, N., Flores, A. C., Marcos, C. Y., Fainboim, H., Theiler, G., Arruvito, L., Williams, F., Middleton, D., and Fainboim, L.
- Published
- 2007
6. KIR receptors and HLA-C in the maintenance of pregnancy
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Flores, A. C., Marcos, C. Y., Paladino, N., Arruvito, L., Williams, F., Middleton, D., and Fainboim, L.
- Published
- 2007
7. Purinergic signaling modulates human visceral adipose inflammatory responses: implications in metabolically unhealthy obesity
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Pandolfi, J, primary, Ferraro, A, additional, Lerner, M, additional, Serrano, J R, additional, Dueck, A, additional, Fainboim, L, additional, and Arruvito, L, additional
- Published
- 2015
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8. ATP-P2X7R pathway activation limits the Tfh cell compartment during pediatric RSV infection.
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Russo C, Raiden S, Algieri S, Bruera MJ, De Carli N, Sarli M, Cairoli H, De Lillo L, Morales I, Seery V, Otero A, Sananez I, Simaz N, Alfiero G, Rubino G, Moya N, Aedo Portela L, Herrero M, Blanco M, Salcedo Pereira M, Ferrero F, Geffner J, and Arruvito L
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- Humans, Male, Infant, Female, Child, Preschool, Signal Transduction, Interleukins metabolism, Interleukins immunology, Antibodies, Viral blood, Antibodies, Viral immunology, Child, Respiratory Syncytial Virus, Human immunology, Respiratory Syncytial Virus Infections immunology, Respiratory Syncytial Virus Infections metabolism, Receptors, Purinergic P2X7 metabolism, Adenosine Triphosphate metabolism, T Follicular Helper Cells immunology, T Follicular Helper Cells metabolism
- Abstract
Background: Follicular helper T cells (Tfh) are pivotal in B cell responses. Activation of the purinergic receptor P2X7 on Tfh cells regulates their activity. We investigated the ATP-P2X7R axis in circulating Tfh (cTfh) cells during Respiratory Syncytial Virus (RSV) infection., Methods: We analyzed two cohorts: children with RSV infection (moderate, n=30; severe, n=21) and healthy children (n=23). We utilized ELISA to quantify the levels of PreF RSV protein-specific IgG antibodies, IL-21 cytokine, and soluble P2X7R (sP2X7R) in both plasma and nasopharyngeal aspirates (NPA). Additionally, luminometry was employed to determine ATP levels in plasma, NPA and supernatant culture. The frequency of cTfh cells, P2X7R expression, and plasmablasts were assessed by flow cytometry. To evaluate apoptosis, proliferation, and IL-21 production by cTfh cells, we cultured PBMCs in the presence of Bz-ATP and/or P2X7R antagonist (KN-62) and a flow cytometry analysis was performed., Results: In children with severe RSV disease, we observed diminished titers of neutralizing anti-PreF IgG antibodies. Additionally, severe infections, compared to moderate cases, were associated with fewer cTfh cells and reduced plasma levels of IL-21. Our investigation revealed dysregulation in the ATP-P2X7R pathway during RSV infection. This was characterized by elevated ATP levels in both plasma and NPA samples, increased expression of P2X7R on cTfh cells, lower levels of sP2X7R, and heightened ATP release from PBMCs upon stimulation, particularly evident in severe cases. Importantly, ATP exposure decreased cTfh proliferative response and IL-21 production, while promoting their apoptosis. The P2X7R antagonist KN-62 mitigated these effects. Furthermore, disease severity positively correlated with ATP levels in plasma and NPA samples and inversely correlated with cTfh frequency., Conclusion: Our findings indicate that activation of the ATP-P2X7R pathway during RSV infection may contribute to limiting the cTfh cell compartment by promoting cell death and dysfunction, ultimately leading to increased disease severity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Russo, Raiden, Algieri, Bruera, De Carli, Sarli, Cairoli, De Lillo, Morales, Seery, Otero, Sananez, Simaz, Alfiero, Rubino, Moya, Aedo Portela, Herrero, Blanco, Salcedo Pereira, Ferrero, Geffner and Arruvito.)
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- 2024
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9. The future of vaccination in Latin America: learning from the COVID-19 pandemic.
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Díaz FE, Arruvito L, and Geffner J
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- Humans, Pandemics prevention & control, Latin America epidemiology, SARS-CoV-2, Vaccination, COVID-19 epidemiology, COVID-19 prevention & control, Vaccines
- Abstract
The SARS-CoV-2 pandemic caused millions of deaths around the world. This dramatic balance requires governments, international organizations, vaccine manufacturers, and the scientific community itself to take stock of what has been done and what could have been done better. In this sense, the tremendous inequity in access to vaccines, the main tool to deal with the pandemic, deserves deep reflection and a set of actions to be carried out by low- and middle-income countries. Among them, the construction of a joint effort to produce their own vaccines and the reconsideration of the bases that govern the intellectual property rights of vaccines and medicines, which harmed equitable access to health, with the consequent loss of many lives that could have been saved., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Published
- 2023
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10. Purinergic signaling pathway in severe COVID-19.
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Arruvito L, Sananez I, Seery V, Russo C, and Geffner J
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- Humans, SARS-CoV-2, Inflammation, Immunity, Signal Transduction, COVID-19
- Abstract
Substantial efforts have been made to understand the immune response during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, in order to identify and characterize risk factors, immune mechanisms responsible for the induction of tissue injury and potential therapeutic targets. Purinergic signaling pathway has shown to modulate the inflammatory processes in the course of several infectious diseases, but its role in the coronavirus disease 2019 (COVID-19) has not been clearly defined. Inflammation is usually associated to the release of ATP from different cell types, starting a cascade of events through the activation of a set of different purinergic receptors. This review summarizes the evidence showing the involvement of the purinergic system in the inflammatory condition that characterizes severe COVID-19., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2023
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11. Persistent symptoms after COVID-19 in children and adolescents from Argentina.
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Seery V, Raiden S, Penedo JMG, Borda M, Herrera L, Uranga M, Marcó Del Pont M, Chirino C, Erramuspe C, Alvarez LS, Lenoir M, Morales LD, Davenport C, Huespe Auchter S, Monsalvo L, Sastoque L, Gavazzi M, Russo C, Sananez I, Pando MLÁ, Laufer N, Muiños R, Ferrero F, Geffner J, and Arruvito L
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- Adult, Humans, Adolescent, Child, Argentina epidemiology, Post-Acute COVID-19 Syndrome, SARS-CoV-2, Cough epidemiology, Cough etiology, COVID-19 complications, COVID-19 epidemiology
- Abstract
Objectives: Although long COVID-19 is widely recognized in adults, less information is available about this condition in children, especially in developing countries. Here, we studied the long-term symptoms of SARS-CoV-2 infection beyond 3 months and the associated risk factors in a pediatric population., Methods: This observational study included 639 Argentinian children and adolescents with previously confirmed COVID-19 from June 2020-June 2021 and 577 children without previous COVID-19. Parents completed a survey about symptoms that their child had for >3 months after the diagnosis of SARS-CoV-2 infection., Results: At least one persistent symptom was observed more frequently in children with previous COVID-19 than in the non-COVID-19 group (34% vs 13%, P <0.0001). SARS-CoV-2 infection increased the risk of headache, dizziness, loss of taste, dyspnea, cough, fatigue, muscle pain, and loss of weight by three- to seven-fold. The loss of smell was only reported in infected children. After controlling for the other variables, older age, symptomatic COVID-19, and comorbidities were independent predictors of long-term symptoms., Conclusions: One-third of children experienced persistent symptoms after COVID-19. Older age, symptomatic infection, and comorbidities were shown to be risk factors for long COVID-19. Pediatric long COVID-19 is a new condition that requires further investigation., Competing Interests: Declaration of competing interest The authors have no competing interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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12. COVID-19: a test for society at a worldwide level.
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Arruvito L
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- Humans, SARS-CoV-2, Societies, Medical, COVID-19
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Competing Interests: None.
- Published
- 2022
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13. Antibody response against SARS-CoV-2 variants of concern in children infected with pre-Omicron variants: An observational cohort study.
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Seery V, Raiden S, Russo C, Borda M, Herrera L, Uranga M, Varese A, Marcó Del Pont M, Chirino C, Erramuspe C, Álvarez LS, Lenoir M, Morales LD, Davenport C, Alarcón Flores A, Huespe Auchter S, Ruiz Y, Monsalvo L, Sastoque L, Gavazzi M, Mazzitelli I, Di Diego F, Longueira Y, Mazzitelli B, Sananez I, De Carli N, Biglione MM, Gómez Penedo JM, Ceballos A, Laufer N, Ferrero F, Geffner J, and Arruvito L
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- Adult, Antibodies, Neutralizing, Antibodies, Viral, Antibody Formation, BNT162 Vaccine, Child, Cohort Studies, Humans, Immunoglobulin G, COVID-19, SARS-CoV-2
- Abstract
Background: Despite that pediatric COVID-19 is usually asymptomatic or mild, SARS-CoV-2 infection typically results in the development of an antibody response. Contradictory observations have been reported when the antibody response of children and adults were compared in terms of strength, specificity and perdurability., Methods: This observational study includes three cohorts infected with SARS-CoV-2 between March 2020-July 2021: unvaccinated infected children (n=115), unvaccinated infected adults (n=62), and vaccinated infected children (n=76). Plasma anti-spike IgG antibodies and neutralising activity against Wuhan, Delta and Omicron variants after 7-17 months post-infection were analysed., Findings: More than 95% of unvaccinated infected children and adults remained seropositive when evaluated at 382-491 and 386-420 days after infection, respectively. Anti-spike IgG titers and plasma neutralising activity against Wuhan, Delta and Omicron variants were higher in children compared to adults. No differences were found when unvaccinated infected children were stratified by age, gender or presence/absence of symptoms in the acute phase of SARS-CoV-2 infection, but a slight decrease in the antibody response was observed in those with comorbidities. Vaccination of previously infected children with two doses of the inactivated BBIBP-CorV or the mRNA vaccines, BNT162b2 and/or mRNA-1273, further increased anti-spike IgG titers and neutralising activity against Wuhan, Delta and Omicron variants., Interpretation: Unvaccinated infected children mount a more potent and sustained antibody response compared with adults, which is significantly increased after vaccination. Further studies including not only the analysis of the immune response but also the effectiveness to prevent reinfections by the different Omicron lineages are required to optimise vaccination strategy in children., Funding: National Agency for Scientific and Technological Promotion from Argentina (PICTO-COVID-SECUELAS-00007 and PMO-BID-PICT2018-2548)., Competing Interests: Declaration of interests The authors have nothing to disclose., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2022
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14. Reply to Kao and Liaw.
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Ochoa V, Díaz FE, Ramirez E, Fentini MC, Carobene M, Geffner J, Arruvito L, and Remes Lenicov F
- Abstract
Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
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- 2022
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15. Extracellular ATP and Imbalance of CD4+ T Cell Compartment in Pediatric COVID-19.
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Russo C, Raiden S, Algieri S, De Carli N, Davenport C, Sarli M, Bruera MJ, Seery V, Sananez I, Simaz N, Bayle C, Nivela V, Ferrero F, Geffner J, and Arruvito L
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- Adenosine Triphosphate metabolism, Adult, CD4-Positive T-Lymphocytes metabolism, Child, Humans, T-Lymphocytes, Regulatory, Th17 Cells, COVID-19, Nuclear Receptor Subfamily 1, Group F, Member 3 metabolism
- Abstract
Severe COVID-19 in children is rare, but the reasons underlying are unclear. Profound alterations in T cell responses have been well characterized in the course of adult severe COVID-19, but little is known about the T cell function in children with COVID-19. Here, we made three major observations in a cohort of symptomatic children with acute COVID-19: 1) a reduced frequency of circulating FoxP3+ regulatory T cells, 2) the prevalence of a TH17 polarizing microenvironment characterized by high plasma levels of IL-6, IL-23, and IL17A, and an increased frequency of CD4+ T cells expressing ROR-γt, the master regulator of TH17 development, and 3) high plasma levels of ATP together with an increased expression of the P2X7 receptor. Moreover, that plasma levels of ATP displayed an inverse correlation with the frequency of regulatory T cells but a positive correlation with the frequency of CD4+ T cells positive for the expression of ROR-γt. Collectively, our data indicate an imbalance in CD4+ T cell profiles during pediatric COVID-19 that might favor the course of inflammatory processes. This finding also suggests a possible role for the extracellular ATP in the acquisition of an inflammatory signature by the T cell compartment offering a novel understanding of the involved mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Russo, Raiden, Algieri, De Carli, Davenport, Sarli, Bruera, Seery, Sananez, Simaz, Bayle, Nivela, Ferrero, Geffner and Arruvito.)
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- 2022
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16. Infants Younger Than 6 Months Infected With SARS-CoV-2 Show the Highest Respiratory Viral Loads.
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Ochoa V, Díaz FE, Ramirez E, Fentini MC, Carobene M, Geffner J, Arruvito L, and Remes Lenicov F
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- Argentina epidemiology, Humans, Infant, COVID-19 diagnosis, Respiratory System virology, SARS-CoV-2 isolation & purification, Viral Load
- Abstract
There is a paucity of reports on the characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in infants, because most studies have grouped infants with older children. We analyzed the viral loads of 45318 SARS-CoV-2-positive nasopharyngeal swab samples obtained in Buenos Aires, Argentina. Infants younger than 6 months presented higher viral loads than any other age group. Children older than 6 months showed significantly lower viral loads, similar to those founds in adults. This observation raises new questions regarding the role of infants in the spreading of SARS-CoV-2 infection., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
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- 2022
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17. Case Report: Relevance of an Accurate Diagnosis and Monitoring of Infective Dermatitis Associated With Human T-Lymphotropic Virus Type 1 in Childhood.
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Benencio P, Ducasa N, Arruvito L, Irurzun I, Praino L, Lamberti M, Beraza M, Berini C, and Biglione M
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Human T-lymphotropic virus type 1 (HTLV-1) is a neglected retrovirus distributed worldwide and the ethiological agent of several pathologies, such as adult T-cell leukemia/lymphoma (ATLL), a chronic myelopathy known as HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and infective dermatitis associated with HTLV-1 (IDH). HTLV-1 presents tropism for CD4
+ T cells and induces deregulation of the cytokine profile. IDH is a severe, chronic superinfected eczema generally associated with Staphylococcus aureus and/or Streptococcus beta haemolyticus infection that responds partially to antibiotic therapy but prompt recurrence develops upon treatment withdrawal. IDH could be a risk factor for progression toward both HAM/TSP and ATLL and, similarly to other diseases associated with HTLV-1, it is sub-diagnosed particularly in non-endemic areas. Here, we present a case of IDH in a young boy living in Buenos Aires with symptoms since 2010, at the age of 5. HTLV-1 infection was suspected and confirmed in 2016. The patient exhibited chronic dermatosis with exudative eruption involving mainly the scalp, retroauricular regions, neck and abdomen. Clinical evaluations, routine laboratory tests, full blood count, and HTLV-1 diagnosis for this case are included., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Benencio, Ducasa, Arruvito, Irurzun, Praino, Lamberti, Beraza, Berini and Biglione.)- Published
- 2021
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18. A poor and delayed anti-SARS-CoV2 IgG response is associated to severe COVID-19 in children.
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Sananez I, Raiden SC, Algieri SC, Uranga M, Grisolía NA, Filippo D, De Carli N, Lalla SD, Cairoli H, Chiolo MJ, Meregalli CN, Cohen E, Mosquera G, Marcó Del Pont M, Giménez LI, Gregorio G, Sarli M, Alcalde AL, Davenport C, Bruera MJ, Simaz N, Pérez MF, Nivela V, Bayle C, Alvarez L, Revetria M, Tuccillo P, Agosta MT, Pérez H, Nova SV, Suárez P, Takata EM, García M, Lattner J, Rolón MJ, Coll P, Salvatori M, Piccardo C, Russo C, Varese A, Seery V, Holgado MP, Polo ML, Ceballos A, Nuñez M, Penedo JMG, Ferrero F, Geffner J, and Arruvito L
- Subjects
- Argentina, COVID-19 blood, Child, Child, Preschool, Cytokines blood, Female, Humans, Infant, Male, SARS-CoV-2 immunology, Systemic Inflammatory Response Syndrome blood, Antibodies, Viral blood, Antibody Formation, COVID-19 complications, COVID-19 immunology, Immunoglobulin G blood, Immunoglobulin M blood, Systemic Inflammatory Response Syndrome immunology
- Abstract
Background: Most children and youth develop mild or asymptomatic disease during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, a very small number of patients suffer severe Coronavirus induced disease 2019 (COVID-19). The reasons underlying these different outcomes remain unknown., Methods: We analyzed three different cohorts: children with acute infection (n=550), convalescent children (n=138), and MIS-C (multisystem inflammatory syndrome in children, n=42). IgG and IgM antibodies to the spike protein of SARS-CoV-2, serum-neutralizing activity, plasma cytokine levels, and the frequency of circulating Follicular T helper cells (cTfh) and plasmablasts were analyzed by conventional methods., Findings: Fifty-eight percent of the children in the acute phase of infection had no detectable antibodies at the time of sampling while a seronegative status was found in 25% and 12% of convalescent and MIS-C children, respectively. When children in the acute phase of the infection were stratified according disease severity, we found that contrasting with the response of children with asymptomatic, mild and moderate disease, children with severe COVID-19 did not develop any detectable response. A defective antibody response was also observed in the convalescent cohort for children with severe disease at the time of admission. This poor antibody response was associated to both, a low frequency of cTfh and a high plasma concentration of inflammatory cytokines., Interpretation: A weak and delayed kinetic of antibody response to SARS-CoV-2 together with a systemic pro-inflammatory profile characterize pediatric severe COVID-19. Because comorbidities are highly prevalent in children with severe COVID-19, further studies are needed to clarify their contribution in the weak antibody response observed in severe disease., Funding: National Agency for Scientific and Technological Promotion from Argentina (IP-COVID-19-0277 and PMO-BID-PICT2018-2548)., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2021
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19. Blood neutrophils from children with COVID-19 exhibit both inflammatory and anti-inflammatory markers.
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Seery V, Raiden SC, Algieri SC, Grisolía NA, Filippo D, De Carli N, Di Lalla S, Cairoli H, Chiolo MJ, Meregalli CN, Gimenez LI, Gregorio G, Sarli M, Alcalde AL, Davenport C, Bruera MJ, Simaz N, Pérez MF, Nivela V, Bayle C, Tuccillo P, Agosta MT, Pérez H, Villa Nova S, Suárez P, Takata EM, García M, Lattner J, Rolón MJ, Coll P, Sananez I, Holgado MP, Ferrero F, Geffner J, and Arruvito L
- Subjects
- Antibodies, Viral blood, Argentina, COVID-19 blood, Case-Control Studies, Child, Child, Preschool, Cytokines blood, Female, Flow Cytometry, Humans, Immunoglobulin G blood, Infant, Male, SARS-CoV-2 immunology, Spike Glycoprotein, Coronavirus immunology, Systemic Inflammatory Response Syndrome blood, Biomarkers blood, COVID-19 immunology, Neutrophils immunology, Systemic Inflammatory Response Syndrome immunology
- Abstract
Background: Perhaps reflecting that children with COVID-19 rarely exhibit severe respiratory symptoms and often remain asymptomatic, little attention has been paid to explore the immune response in pediatric COVID-19. Here, we analyzed the phenotype and function of circulating neutrophils from children with COVID-19., Methods: An observational study including 182 children with COVID-19, 21 children with multisystem inflammatory syndrome (MIS-C), and 40 healthy children was performed in Buenos Aires, Argentina. Neutrophil phenotype was analyzed by flow cytometry in blood samples. Cytokine production, plasma levels of IgG antibodies directed to the spike protein of SARS-CoV-2 and citrullinated histone H3 were measured by ELISA. Cell-free DNA was quantified by fluorometry., Findings: Compared with healthy controls, neutrophils from children with COVID-19 showed a lower expression of CD11b, CD66b, and L-selectin but a higher expression of the activation markers HLA-DR, CD64 and PECAM-1 and the inhibitory receptors LAIR-1 and PD-L1. No differences in the production of cytokines and NETs were observed. Interestingly, the expression of CD64 in neutrophils and the serum concentration of IgG antibodies directed to the spike protein of SARS-CoV-2 distinguished asymptomatic from mild and moderate COVID-19., Interpretation: Acute lung injury is a prominent feature of severe COVID-19 in adults. A low expression of adhesion molecules together with a high expression of inhibitory receptors in neutrophils from children with COVID-19 might prevent tissue infiltration by neutrophils preserving lung function., Funding: This study was supported by the Ministry of Science and Technology (National Agency for Scientific and Technological Promotion, IP-COVID-19-0277 and PMO BID PICT 2018-2548), and University of Buenos Aires from Argentina (20020170100573BA)., Competing Interests: Declaration of Competing Interest The authors have declared that no conflict of interest exists., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2021
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20. Fcγ Receptor IIa (FCGR2A) Polymorphism Is Associated With Severe Respiratory Syncytial Virus Disease in Argentinian Infants.
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Holgado MP, Raiden S, Sananez I, Seery V, De Lillo L, Maldonado LL, Kamenetzky L, Geffner J, and Arruvito L
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- Child, Humans, Infant, Polymorphism, Genetic, Respiratory Syncytial Viruses, Receptors, IgG genetics, Respiratory Syncytial Virus Infections genetics
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Background: Most patients with respiratory syncytial virus (RSV) infection requiring hospitalization have no risk factors for severe disease. Genetic variation in the receptor for the Fc portion of IgG (FcγR) determines their affinity for IgG subclasses driving innate and adaptive antiviral immunity. We investigated the relationship between FcγRIIa-H131R polymorphism and RSV disease., Methods: Blood samples were collected from 182 infants ≤24-month-old (50 uninfected, 114 RSV-infected with moderate course and 18 suffering severe disease). FcγRIIa-H131R SNP genotypic frequencies (HH, HR, RR) and anti-RSV IgG1, IgG2 and IgG3 levels were studied., Results: Genotypic frequencies for FcγRIIa-H131R SNP were comparable between uninfected and RSV-infected infants. In contrast, we found a significant higher frequency of HH genotype in severe RSV-infected children compared to moderate patients. Among severe group, HH infants presented more factors associated to severity than HR or RR patients did. Furthermore, compared to moderate RSV-infected infants, severe patients showed higher levels of anti-RSV IgG1 and IgG3., Conclusions: We found an association between an FcγRIIa (H131) polymorphism and severe RSV disease, which points towards a critical role for interactions between FcγRs and immune complexes in RSV pathogenesis. This genetic factor could also predict the worse outcome and identify those infants at risk during hospitalization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Holgado, Raiden, Sananez, Seery, De Lillo, Maldonado, Kamenetzky, Geffner and Arruvito.)
- Published
- 2020
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21. Upregulation of CD32 in T Cells from Infants with Severe Respiratory Syncytial Virus Disease: A New Costimulatory Pathway?
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Sananez I, Raiden S, Holgado MP, Seery V, De Lillo L, Davenport C, Ferrero F, Peeples ME, Geffner J, and Arruvito L
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- Female, Humans, Infant, Male, Respiratory Syncytial Viruses pathogenicity, CD4-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes metabolism, Receptors, IgG metabolism, Respiratory Syncytial Virus Infections metabolism, Up-Regulation physiology
- Published
- 2020
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22. CD32 Ligation Promotes the Activation of CD4 + T Cells.
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Holgado MP, Sananez I, Raiden S, Geffner JR, and Arruvito L
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- Adult, CD4-Positive T-Lymphocytes cytology, Female, Humans, Lymphocyte Activation, Male, CD4-Positive T-Lymphocytes immunology, Immunologic Capping, Receptors, IgG immunology
- Abstract
Low affinity receptors for the Fc portion of IgG (FcγRs) represent a critical link between innate and adaptive immunity. Immune complexes (ICs) are the natural ligands for low affinity FcγRs, and high levels of ICs are usually detected in both, chronic viral infections and autoimmune diseases. The expression and function of FcγRs in myeloid cells, NK cells and B cells have been well characterized. By contrast, there are controversial reports about the expression and function of FcγRs in T cells. Here, we demonstrated that ~2% of resting CD4+ T cells express cell surface FcγRII (CD32). Analysis of CD32 expression in permeabilized cells revealed an increased proportion of CD4+CD32+ T cells (~9%), indicating that CD4+ T cells store a CD32 cytoplasmic pool. Activation of CD4+ T cells markedly increased the expression of CD32 either at the cell surface or intracellularly. Analysis of CD32 mRNA transcripts in activated CD4+ T cells revealed the presence of both, the stimulatory FcγRIIa (CD32a) and the inhibitory FcγRIIb (CD32b) isoforms of CD32, being the CD32a:CD32b mRNA ratio ~5:1. Consistent with this finding, we found not only that CD4+ T cells bind aggregated IgG, used as an IC model, but also that CD32 ligation by specific mAb induced a strong calcium transient in CD4+ T cells. Moreover, we found that pretreatment of CD4+ T cells with immobilized IgG as well as cross-linking of CD32 by specific antibodies increased both, the proliferative response of CD4+ T cells and the release of a wide pattern of cytokines (IL-2, IL-5, IL-10, IL-17, IFN-γ, and TNF-α) triggered by either PHA or anti-CD3 mAb. Collectively, our results indicate that ligation of CD32 promotes the activation of CD4+ T cells. These findings suggest that ICs might contribute to the perpetuation of chronic inflammatory responses by virtue of its ability to directly interact with CD4+ T cells through CD32a, promoting the activation of T cells into different inflammatory profiles.
- Published
- 2018
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23. Dampening of IL-2 Function in Infants With Severe Respiratory Syncytial Virus Disease.
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Sananez I, Raiden S, Erra-Díaz F, De Lillo L, Holgado MP, Geffner J, and Arruvito L
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- Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Humans, Infant, Interleukin-2 Receptor alpha Subunit blood, Male, Immunologic Factors metabolism, Interleukin-2 metabolism, Respiratory Syncytial Virus Infections pathology, T-Lymphocytes, Regulatory immunology
- Abstract
Background: FOXP3+ regulatory T cells (Tregs) restrain the destructive potential of the immune system. We have previously reported a pronounced reduction in circulating Tregs in infants with severe respiratory syncytial virus (RSV) disease. Because interleukin-2 (IL-2) is critical for Treg growth, survival, and activity, we here analyzed IL-2 production and function in RSV-infected infants., Methods: Phenotype, proliferation, IL-2 production, and IL-2 signaling in CD4+ T cells were analyzed by flow cytometry. Serum soluble CD25 levels were quantified by ELISA., Results: CD4+ T cells from RSV-infected infants produced lower amounts of IL-2 and showed a reduced proliferative response compared with healthy infants. IL-2 increased CD4+ T-cell proliferation and FOXP3 expression in both healthy and RSV-infected infants. However, although IL-2 induced a similar pattern of STAT5 phosphorylation, the proliferative response of CD4+ T cells and the expression of FOXP3+ remained significantly lower in RSV-infected infants. Interestingly, we found a negative correlation between disease severity and both the production of IL-2 by CD4+ T cells and the ability of exogenous IL-2 to restore the pool of FOXP3+CD4+ T cells., Conclusions: A reduced ability to produce IL-2 and a limited response to this cytokine may affect the function of CD4+ T cells in RSV-infected infants.
- Published
- 2018
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24. Respiratory Syncytial Virus (RSV) Infects CD4+ T Cells: Frequency of Circulating CD4+ RSV+ T Cells as a Marker of Disease Severity in Young Children.
- Author
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Raiden S, Sananez I, Remes-Lenicov F, Pandolfi J, Romero C, De Lillo L, Ceballos A, Geffner J, and Arruvito L
- Subjects
- Adult, Biomarkers blood, CD4-Positive T-Lymphocytes virology, CD8-Positive T-Lymphocytes virology, Cell Line, Female, Fetal Blood cytology, Flow Cytometry, Humans, Infant, Infant, Newborn, Interferon-gamma immunology, Interleukin-2 immunology, Male, Respiratory Syncytial Virus, Human, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Respiratory Syncytial Virus Infections immunology
- Abstract
Background: Although human airway epithelial cells are the main target of respiratory syncytial virus (RSV), it also infects immune cells, such as macrophages and B cells. Whether T cells are permissive to RSV infection is unknown. We sought to analyze the permissiveness of CD4+ T cells to RSV infection., Methods: CD4+ and CD8+ T cells from cord blood, healthy young children, and adults were challenged by RSV or cocultured with infected HEp-2 cells. Infection, phenotype, and cytokine production by T cells were analyzed by flow cytometry or enzyme-linked immunosorbent assay. Expression of RSV antigens by circulating CD4+ T cells from infected children was analyzed by flow cytometry, and disease severity was defined by standard criteria., Results: CD4+ and CD8+ T cells were productively infected by RSV. Infection decreased interleukin 2 and interferon γ production as well as the expression of CD25 and Ki-67 by activated CD4+ T cells. Respiratory syncytial virus antigens were detected in circulating CD4+ and CD8+ T cells during severe RSV infection of young children. Interestingly, the frequency of CD4+ RSV+ T cells positively correlated with disease severity., Conclusions: Respiratory syncytial virus infects CD4+ and CD8+ T cells and compromises T-cell function. The frequency of circulating CD4+ RSV+ T cells might represent a novel marker of severe infection., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2017
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25. ATP-Induced Inflammation Drives Tissue-Resident Th17 Cells in Metabolically Unhealthy Obesity.
- Author
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Pandolfi JB, Ferraro AA, Sananez I, Gancedo MC, Baz P, Billordo LA, Fainboim L, and Arruvito L
- Subjects
- Adult, Antigens, CD biosynthesis, Apoptosis physiology, Apyrase biosynthesis, Cellular Microenvironment immunology, Female, Humans, Inflammation immunology, Interleukin-17 metabolism, Interleukin-1beta metabolism, Interleukin-6 metabolism, Intra-Abdominal Fat cytology, Intra-Abdominal Fat pathology, Male, Nuclear Receptor Subfamily 1, Group F, Member 3 metabolism, Obesity pathology, Receptors, Interleukin metabolism, Th17 Cells metabolism, Adenosine Triphosphate metabolism, Intra-Abdominal Fat immunology, Obesity immunology, Receptors, Purinergic P2X7 metabolism, Th17 Cells immunology
- Abstract
Obesity-induced inflammation is conducted by a metabolic pathway, which eventually causes activation of specialized immune cells and leads to an unresolved inflammatory response within the tissue. For this reason, it is critically important to determine how hypertrophic fat tissue alters T cell balance to drive inflammation. In this study, we identify the purinergic signaling as a novel mechanism driving the adaptive Th17 response in human visceral adipose tissue (VAT) of metabolically unhealthy obese patients. We demonstrate that ATP acting via the P2X7 receptor pathway promotes a Th17 polarizing microenvironment with high levels of IL-1β, IL-6, and IL-17 in VAT explants from lean donors. Moreover, in vitro blockade of the P2X7 receptor abrogates the levels of these cytokines. These findings are consistent with a greater frequency of Th17 cells in tissue from metabolically unhealthy obese donors, revealed not only by the presence of a baseline Th17-promoting milieu, but also by the higher expression of steadily recognized Th17 markers, such as RORC, IL-17 cytokine, and IL-23R, in comparison with metabolically healthy obese and lean donors. In addition, we demonstrate that CD39 expression on CD4(+)effector T cells represents a novel Th17 marker in the inflamed VAT, which also confers protection against ATP-induced cell death. The manipulation of the purinergic signaling might represent a new therapeutic target to shift the CD4(+)T cell balance under inflammatory conditions., (Copyright © 2016 by The American Association of Immunologists, Inc.)
- Published
- 2016
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- View/download PDF
26. Host response to respiratory syncytial virus infection.
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Arruvito L, Raiden S, and Geffner J
- Subjects
- Adaptive Immunity, Animals, Disease Models, Animal, Host-Pathogen Interactions, Humans, Immunity, Innate, Infant, Mice, Respiratory Syncytial Virus Infections physiopathology, Respiratory Syncytial Viruses isolation & purification, T-Lymphocytes, Regulatory immunology, Respiratory Syncytial Virus Infections immunology, Respiratory Syncytial Virus Vaccines immunology, Respiratory Syncytial Viruses immunology
- Abstract
Purpose of Review: Respiratory syncytial virus (RSV) infection is the leading cause of bronchiolitis and hospitalization in young infants and causes 100, 000-200, 000 deaths annually. There is still no licensed vaccine against RSV infection and the therapeutic options are mainly supportive. Despite almost six decades of research, important knowledge gaps remain with respect to the characterization of immune mechanisms responsible for protection and pathogenesis, as well as to the identification of risk factors that predict the severity of infection., Recent Findings: Observations made in mouse models and young children suggest that the early innate immune response plays a major role in the pathogenesis of bronchiolitis due to RSV infection. Recent studies have improved our understanding of the role of the adaptive immune response mediated by TH1, TH2, TH17, regulatory T cells, and CD8 T cells in the pathogenesis and resolution of RSV infection. Moreover, investigations performed in the last years have made important contributions to our knowledge of the immune response in young children, the principal risk group for severe disease., Summary: A comprehensive understanding of how the protective and deleterious immune response during the course of RSV infection is induced in young children remains a challenge over the coming years.
- Published
- 2015
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27. Identification and clinical relevance of naturally occurring human CD8+HLA-DR+ regulatory T cells.
- Author
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Arruvito L, Payaslián F, Baz P, Podhorzer A, Billordo A, Pandolfi J, Semeniuk G, Arribalzaga E, and Fainboim L
- Subjects
- Aged, Aged, 80 and over, CD8-Positive T-Lymphocytes immunology, CTLA-4 Antigen immunology, CTLA-4 Antigen metabolism, Carcinoma, Non-Small-Cell Lung immunology, Carcinoma, Non-Small-Cell Lung pathology, Cell Communication, Cell Proliferation drug effects, Female, Fetal Blood cytology, HLA-DR Antigens immunology, Humans, Immunomodulation, Immunophenotyping, Infant, Newborn, Interleukin-2 pharmacology, Leukocytes, Mononuclear immunology, Leukocytes, Mononuclear metabolism, Lymphocyte Activation immunology, Lymphocyte Count, Male, Middle Aged, T-Lymphocyte Subsets immunology, T-Lymphocytes, Regulatory immunology, CD8-Positive T-Lymphocytes metabolism, HLA-DR Antigens metabolism, Phenotype, T-Lymphocyte Subsets metabolism, T-Lymphocytes, Regulatory metabolism
- Abstract
The lack of responsiveness to self and non-self Ags is normally maintained by multiple mechanisms, including the suppressive activities of several T cell subsets. In this study, we show that CD8(+) T cells from both adult peripheral blood and umbilical cord blood mononuclear cells constitutively expressing HLA-DR represent a natural human CD8(+) regulatory T cell subset. Their suppressive effect appears to be cell-to-cell contact dependent and may involve CTLA-4 signaling between neighboring T cells. These regulatory T cells can be expanded in vitro and exhibit a suppressive capacity similar to that observed in ex vivo CD8(+)HLA-DR(+) T cells. The high frequency of CD8(+)HLA-DR(+) T cells that we detected in patients with non-small cell lung cancer deserves further work to confirm their putative suppressor effect within the tumor., (Copyright © 2014 by The American Association of Immunologists, Inc.)
- Published
- 2014
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28. Depletion of circulating regulatory T cells during severe respiratory syncytial virus infection in young children.
- Author
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Raiden S, Pandolfi J, Payasliàn F, Anderson M, Rivarola N, Ferrero F, Urtasun M, Fainboim L, Geffner J, and Arruvito L
- Subjects
- Bronchiolitis, Viral blood, Case-Control Studies, Female, Flow Cytometry, Humans, Infant, Infant, Newborn, Lymphocyte Count, Male, Respiratory Syncytial Virus Infections blood, Severity of Illness Index, Bronchiolitis, Viral immunology, Respiratory Syncytial Virus Infections immunology, T-Lymphocytes, Regulatory metabolism
- Published
- 2014
- Full Text
- View/download PDF
29. Regulatory and effector T-cells are differentially modulated by Dexamethasone.
- Author
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Pandolfi J, Baz P, Fernández P, Discianni Lupi A, Payaslián F, Billordo LA, Fainboim L, and Arruvito L
- Subjects
- Adult, Apoptosis drug effects, Cell Proliferation drug effects, Cell Survival drug effects, Cell Survival immunology, Female, Forkhead Transcription Factors metabolism, Gene Expression, Homeostasis, Humans, Interleukin-2 pharmacology, Interleukin-2 Receptor alpha Subunit metabolism, Lymphocyte Activation drug effects, Male, Organ Specificity, T-Lymphocytes, Cytotoxic cytology, T-Lymphocytes, Cytotoxic immunology, T-Lymphocytes, Regulatory cytology, T-Lymphocytes, Regulatory immunology, Anti-Inflammatory Agents pharmacology, Dexamethasone pharmacology, T-Lymphocytes, Cytotoxic drug effects, T-Lymphocytes, Regulatory drug effects
- Abstract
It is assumed that the ratio between effector T cells (Teff) and regulatory T cells (Tregs) controls the immune reactivity within the T-cell compartment. The purpose of this study was to investigate if Dexamethasone (Dex) affects Teff and Tregs subsets. Dex induced on Tregs a dose and time-dependent apoptosis which resulted in a relative increase of Teff. After TCR activation, Dex induced a strong proliferative inhibition of Teff, but a weaker proliferative inhibition on Tregs. These effects were modulated by IL-2, which not only restored the proliferative response, but also prevented Dex-induced apoptosis. The highest dose of IL-2 prevented apoptosis on all FOXP3+CD4+ T cells. Meanwhile, the lowest dose only rescued activated Tregs (aTregs), probably related to their CD25 higher expression. Because Dex did not affect the suppressor capacity of aTregs either, our results support the notion that under Dex treatment, the regulatory T-cell compartment maintains its homeostasis., (© 2013.)
- Published
- 2013
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30. Analysis of suppressor and non-suppressor FOXP3+ T cells in HIV-1-infected patients.
- Author
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Arruvito L, Sabatté J, Pandolfi J, Baz P, Billordo LA, Lasala MB, Salomón H, Geffner J, and Fainboim L
- Subjects
- Adult, Aged, Cell Count, Cohort Studies, Cytokines biosynthesis, Disease Susceptibility, Flow Cytometry, HIV Infections pathology, Humans, Lymphocyte Subsets immunology, Middle Aged, T-Lymphocytes, Regulatory immunology, Tissue Donors, Young Adult, CD4-Positive T-Lymphocytes immunology, Forkhead Transcription Factors metabolism, HIV Infections immunology, HIV-1 immunology
- Abstract
Recently, it was shown that peripheral blood FOXP3+CD4+ T cells are composed of three phenotypic and functionally distinct subpopulations. Two of them having in vitro suppressive effects were characterized as resting Treg cells (rTregs) and activated Treg cells (aTregs). A third subset, identified as FOXP3+ non-Tregs, does not display any suppressor activity and produce high levels of Th1 and Th17 cytokines upon stimulation. In the present study we focus on the characteristics of these three subsets of FOXP3+CD4+ T cells in untreated HIV-1-infected patients. We found that the absolute counts of rTregs, aTregs and FOXP3+ non-Tregs were reduced in HIV-1 patients compared with healthy donors. The relative frequency of rTregs and aTregs was similar in HIV-1 patients and healthy donors, while the frequency of FOXP3+ non-Tregs was significantly higher in HIV-1 patients, reaching a maximum in those patients with the lower values of CD4 counts. Contrasting with the observations made in FOXP3- CD4+ T cells, we did not find a negative correlation between the number of rTregs, aTregs or FOXP3+ non-Tregs and virus load. Studies performed with either whole PBMCs or sorted aTregs and FOXP3+ non-Tregs cells showed that these two populations of FOXP3+ T cells were highly permissive to HIV-1 infection. Upon infection, FOXP3+ non-Tregs markedly down-regulates its capacity to produce Th1 and Th17 cytokines, however, they retain the ability to produce substantial amounts of Th2 cytokines. This suggests that FOXP3+ non-Tregs might contribute to the polarization of CD4+ T cells into a Th2 profile, predictive of a poor outcome of HIV-1-infected patients.
- Published
- 2012
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31. A physiological role for inducible FOXP3(+) Treg cells. Lessons from women with reproductive failure.
- Author
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Arruvito L, Sotelo AI, Billordo A, and Fainboim L
- Subjects
- Adult, Case-Control Studies, Female, Follicular Phase immunology, Forkhead Transcription Factors metabolism, Humans, Immune Tolerance, In Vitro Techniques, Interleukin-2 metabolism, Interleukin-6 metabolism, Isoantigens administration & dosage, Kinetics, Lymphocyte Activation, Lymphocyte Culture Test, Mixed, Male, Middle Aged, Pregnancy, STAT5 Transcription Factor metabolism, Signal Transduction, Transforming Growth Factor beta metabolism, Young Adult, Abortion, Habitual immunology, T-Lymphocytes, Regulatory immunology
- Abstract
We have previously shown a decreased frequency and function of Tregs in women suffering from recurrent spontaneous abortions (RSA). In the current study, we first investigated the expression of FOXP3 after T-cell activation. We observed that expression of FOXP3 in activated PBMCs was already present above baseline before any cell division, indicating that it was induced in cells that were previously negative for this transcription factor. Because RSA women showed a more limited expansion of FOXP3-positive cells, we next assessed the role of IL-2 signaling through STAT5, which is known to be required for generation of inducible Tregs (iTregs). We demonstrated not only that TGF-beta and IL-2 were diminished but also that the IL-2-STAT-5 signaling axis was down regulated in RSA women. Finally, in addition to a limited FOXP3(+) cells expansion in vitro, iTregs from RSA women showed a strikingly lower suppressor activity., (Copyright 2010. Published by Elsevier Inc.)
- Published
- 2010
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- View/download PDF
32. The most severe forms of type I autoimmune hepatitis are associated with genetically determined levels of TGF-beta1.
- Author
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Paladino N, Flores AC, Fainboim H, Schroder T, Cuarterolo M, Lezama C, Ballerga EG, Levi D, Tanno H, Costanzo G, Arruvito L, and Fainboim L
- Subjects
- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Alleles, Child, Child, Preschool, Codon, DNA blood, DNA genetics, Female, Genotype, Humans, Infant, Male, Middle Aged, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Young Adult, Hepatitis, Autoimmune genetics, Hepatitis, Autoimmune immunology, Transforming Growth Factor beta genetics, Transforming Growth Factor beta immunology
- Abstract
We previously reported that paediatric (PAH) and adult (AAH) forms of type I autoimmune hepatitis (AH) have different HLA-associations and clinical outcome. In the present study we investigated the role of TGF-beta1 genetic polymorphisms in the different outcome of PAH and AAH. We found a significant increase of "high producer" 25GG genotype in PAH and 10CC in AAH. Low inflammation and low fibrosis in AAH was associated with the increase of codon 10CC (high producer) and codon 25CC (low producer) genotypes. The analysis in AAH of the two positions-haplotypes revealed that combined presence of 25GG and 10CC seems to neutralize the 10CC effect which remained in AAH having the 10CC(+)-25GG(-) haplotype. Altogether these results may explain, at least partially, the different clinical outcome of AAH and PAH., (Published by Elsevier Inc.)
- Published
- 2010
- Full Text
- View/download PDF
33. NK cells expressing a progesterone receptor are susceptible to progesterone-induced apoptosis.
- Author
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Arruvito L, Giulianelli S, Flores AC, Paladino N, Barboza M, Lanari C, and Fainboim L
- Subjects
- Adult, Female, Humans, Interferon-gamma immunology, Interferon-gamma metabolism, Interleukin-12 immunology, Interleukin-12 metabolism, Killer Cells, Natural drug effects, Killer Cells, Natural immunology, Lymphocyte Subsets drug effects, Lymphocyte Subsets immunology, Male, Mifepristone pharmacology, Signal Transduction, Apoptosis, Killer Cells, Natural metabolism, Lymphocyte Subsets metabolism, Progesterone metabolism, Receptors, Progesterone metabolism
- Abstract
It has been proposed that progesterone (P4) induces the suppression of immune responses, particularly during pregnancy. However, knowledge about the mechanisms involved has remained largely elusive. We demonstrate herein that peripheral blood NK (PBNK) cells express both classical progesterone receptor (PR) isoforms and are specifically affected by the actions of P4 through two apparently independent mechanisms. Progesterone induces caspase-dependent PBNK cell death, which is reversed by two different anti-progestins, ZK 98.299 and RU 486, supporting the involvement of classical PR isoforms. It was suggested that CD56(bright)CD16(-) killer Ig-like receptor (KIR)(-) NK cells might represent precursor cells, which, upon activation, acquire the features of a more mature NK subset expressing KIR receptors. The present study demonstrates that PR expression seems to be restricted to more mature KIR(+) PBNK cells. The expression of PR had a functional counterpart in the suppressive effect of P4 on IL-12-induced IFN-gamma secretion. This cytokine suppression was mainly observed in KIR(+) PBNK cells, without affecting the high secretion of IFN-gamma by CD56(bright) PBNK cells. The lack of PR expression on CD56(bright)KIR(-) PBNK cells provides an additional phenotypic marker to test the idea that they might represent the PBNK precursors selectively recruited into the endometrium where they differentiate to become the uterine NK cells. Additionally, these findings may be relevant to NK cell function in viral immunity, human reproduction, and tumor immunity.
- Published
- 2008
- Full Text
- View/download PDF
34. Expansion of CD4+CD25+and FOXP3+ regulatory T cells during the follicular phase of the menstrual cycle: implications for human reproduction.
- Author
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Arruvito L, Sanz M, Banham AH, and Fainboim L
- Subjects
- Abortion, Habitual blood, Adult, Aged, Autoimmune Diseases blood, Autoimmune Diseases immunology, Estradiol blood, Female, Follicular Phase blood, Forkhead Transcription Factors blood, Humans, Luteal Phase blood, Luteal Phase immunology, Male, Middle Aged, Postmenopause blood, Postmenopause immunology, Pregnancy, T-Lymphocytes, Regulatory metabolism, Abortion, Habitual immunology, Follicular Phase immunology, Forkhead Transcription Factors immunology, T-Lymphocytes, Regulatory immunology
- Abstract
Regulatory T cells (Tregs) are thought to affect the severity of various infectious and autoimmune diseases. The incidence of autoimmune disease is higher in fertile women than in men. Thus, we investigated whether Treg numbers were modulated during the menstrual cycle by sex hormones. In fertile nonpregnant women, we detected an expansion of CD4(+)CD25(+)FOXP3(+) Tregs in the late follicular phase of the menstrual cycle. This increase was tightly correlated with serum levels of estradiol and was followed by a dramatic decrease in Treg numbers at the luteal phase. Women who have had recurrent spontaneous abortions (RSA) showed similarly low numbers of Tregs at both the follicular and luteal phases, comparable to numbers we observed in postmenopausal women. In addition to decreased numbers, Tregs from women with RSA were also functionally deficient, as higher numbers were required to exert a similar magnitude of suppression to CD4(+)CD25(+)FOXP3(+) cells from fertile women. Consequently, reproductive failure might result from the inability of Tregs in women with RSA to expand during the preimplantatory phase combined with their lower functional capacity. Additionally, the modulation of Treg numbers we observed in fertile women suggests that the stage of the menstrual cycle should be taken into account when Treg numbers are investigated clinically.
- Published
- 2007
- Full Text
- View/download PDF
35. Cytokines and chronic liver disease.
- Author
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Fainboim L, Cherñavsky A, Paladino N, Flores AC, and Arruvito L
- Subjects
- Animals, Autoantigens immunology, Chronic Disease, Dendritic Cells pathology, Endothelial Cells pathology, Hepatovirus immunology, Humans, Kupffer Cells pathology, Liver immunology, Liver injuries, Liver pathology, Liver Diseases pathology, Organ Specificity immunology, Cytokines immunology, Dendritic Cells immunology, Endothelial Cells immunology, Immune Tolerance, Kupffer Cells immunology, Liver Diseases immunology
- Abstract
From an immunological point of view, the healthy liver has been usually associated with the phenomenon of tolerance. A microenvironment of regulatory cytokines produced by liver Kuppfer cells and liver sinusoidal endothelial cells has contributed, together with resident dendritic cells, to generate a tolerogenic environment in this tissue. In this review we discussed the intrahepatic responses to different sorts of liver injury, such as hepatotrophic viruses, alcohol or putative self-antigens. In each case we analyzed the impact of different cytokines in the clinical outcome of the different pathological situations.
- Published
- 2007
- Full Text
- View/download PDF
36. [Purulent pericarditis with pericardial tamponade caused by Streptococcus agalactiae and Salmonella enterica no typhi].
- Author
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Arruvito L, Ber MG, and Martínez Martínez JA
- Subjects
- Aged, Cardiac Tamponade diagnosis, Cross Infection microbiology, Fatal Outcome, Humans, Male, Pericarditis diagnosis, Pneumonia microbiology, Salmonella Infections complications, Shock, Septic microbiology, Streptococcal Infections complications, Cardiac Tamponade microbiology, Pericarditis microbiology, Salmonella enterica isolation & purification, Streptococcus agalactiae isolation & purification
- Abstract
Purulent pericarditis (PP) is an uncommon condition with high mortality. In the preantibiotic period, Staphyloccocus aureus and Streptococcus pneumoniae were the most common etiologic agents. We describe the case of a 75-year old man with septic shock, PP and cardiac tamponade caused by Streptococcus agalactiae and Salmonella enterica no-typhi. To our knowledge this association of pathogenic organisms has not been previously reported in the literature. The pathogenesis is here reviewed, and in our patient presumably, purulent pericarditis occurred via hematogeneus spread undergoing upper gastrointestinal endoscopy. The patient's course was complicated and he died on 34th hospital day. After this case report it is considered that differential etiologic diagnosis of PP should include these agents, especially in immunodepressed patients with predisposing factors.
- Published
- 2004
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