120 results on '"Dutra, Walderez O."'
Search Results
102. Activated T and B lymphocytes in peripheral blood of patients with Chagas' disease
- Author
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Dutra, Walderez O., primary, Martins-Filho, Olindo A., additional, Can¸ado, Jose R., additional, Pinto-Dias, Joao Carlos, additional, Brener, Zigman, additional, Freeman, George L., additional, Colley, Daniel G., additional, Gazzinelll, Giovanni, additional, and Parra, Jupara C., additional
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- 1994
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103. Trypanosoma cruzi: Populations bearing opposite virulence induce differential expansion of circulating CD3+CD4−CD8− T cells and cytokine serum levels in young and adult rats
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Nagib, Patrícia R.A., Dutra, Walderez O., Chiari, Egler, and Machado, Conceição R.S.
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CHAGAS' disease , *TRYPANOSOMA cruzi , *T cells , *TRYPANOSOMA - Abstract
Abstract: The JG strain is the least virulent while the CL-Brener clone is one of the most virulent Trypanosoma cruzi populations in young rats. In this study, we determined that the parasitemia peak values in CL-Brener clone-infected adult rats were 50-fold lower than in young rats and that mortality was null as compared to 45% death in young rats. Low parasitemia, milder and sustained myocarditis and myositis characterized JG infections. CL-Brener clone caused a significantly higher production of pro-inflammatory cytokines and higher expansion of CD3+CD4−CD8−, double-negative (DN) T cells, during the acute phase in both adult and young rats. DN T cell frequencies correlated with IFN-γ levels. These findings may explain the higher inflammation and fast acute phase resolution in CL-Brener infection. In young rats, IL-10 levels were similar in both infections. The IL-10/IFN-γ ratio was higher in JG acute infection in accordance with the milder inflammation and parasite persistence leading to a chronic phase. In conclusion, virulence and pathogenicity depend on T. cruzi ability to induce expansion of DN T cells and production of specific cytokines. [Copyright &y& Elsevier]
- Published
- 2007
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104. Polarized Th2 like cells, in the absence of Th0 cells, are responsible for lymphocyte produced IL-4 in high IgE-producer schistosomiasis patients.
- Author
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Dutra, Walderez O., Correa-Oliveira, Rodrigo, Dunne, David, Cecchini, Luiza Fosenca, Fraga, Lúcia, Roberts, Morven, Soares-Silveira, Alda Maria, Webster, Michelle, Yssel, Hans, and Gollob, Kenneth J.
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INTERLEUKIN-4 , *INTERFERONS , *INTERLEUKIN-5 , *INTERLEUKIN-2 , *LYMPHOCYTES , *SCHISTOSOMIASIS , *IMMUNOGLOBULIN E , *CELL proliferation , *PATIENTS - Abstract
Background: Human resistance to re-infection with S. mansoni is correlated with high levels of anti-soluble adult worm antigens (SWAP) IgE. Although it has been shown that IL-4 and IL-5 are crucial in establishing IgE responses in vitro, the active in vivo production of these cytokines by T cells, and the degree of polarization of Th2 vs. Th0 in human schistosomiasis is not known. To address this question, we determined the frequency of IL-4 and IFN-γ or IL-5 and IL-2 producing lymphocytes from schistosomiasis patients with high or low levels of IgE anti-SWAP. Results: Our analysis showed that high and low IgE-producers responded equally to schistosomiasis antigens as determined by proliferation. Moreover, patients from both groups displayed similar percentages of circulating lymphocytes. However, high IgE-producers had an increased percentage of activated CD4+ T cells as compared to the low IgE-producers. Moreover, intracellular cytokine analysis, after short-term stimulation with anti-CD3/CD28 mAbs, showed that IgE high-producers display an increase in the percentage of T lymphocytes expressing IL-4 and IL-5 as compared to IgE low-responders. A coordinate control of the frequency of IL-4 and IL-5 producing lymphocytes in IgE high, but not IgE low-responders, was observed. Conclusions: High IgE phenotype human schistosomiasis patients exhibit a coordinate regulation of IL-4 and IL-5 producing cells and the lymphocyte derived IL-4 comes from true polarized Th2 like cells, in the absence of measurable Th0 cells as measured by co-production of IL-4 and IFN-γ. [ABSTRACT FROM AUTHOR]
- Published
- 2002
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105. Trypanosoma cruzi-Induced Activation of Functionally Distinct αβ and γδ CD4−CD8−T Cells in Individuals with Polar Forms of Chagas' Disease
- Author
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Villani, Fernanda Nobre Amaral, da Costa Rocha, Manoel Otávio, Nunes, Maria do Carmo Pereira, Antonelli, Lis Ribeiro do Valle, Magalhães, Luisa Mourão Dias, dos Santos, Janete Soares Coelho, Gollob, Kenneth J., and Dutra, Walderez O.
- Abstract
ABSTRACTCD4−CD8−(double-negative [DN]) T cells have recently been shown to display important immunological functions in human diseases. They express γδ or αβ T-cell receptors that recognize lipid/glycolipid antigens presented via the nonclassical major histocompatibility complex molecules of the CD1 family. We recently demonstrated that while αβ DN T cells serve primarily to express inflammatory cytokines, γδ DN T cells express mainly interleukin-10 (IL-10) in patients with cutaneous leishmaniasis. We also demonstrated a correlation between DN T cells and the expression of gamma interferon in the acute phase of Trypanosoma cruziexperimental infection. In this work, we sought to investigate whether αβ or γδ DN T cells display distinct immunoregulatory potentials in patients with polar forms of human Chagas' disease. Our data showed that in vitroinfection with T. cruzileads to expansion of DN T cells in patients with the indeterminate and severe cardiac clinical forms of the disease. However, while αβ DN T cells primarily produce inflammatory cytokines in both forms of the disease, γδ DN T cells display a marked, significant increase in antigen-specific IL-10 expression in indeterminate patients relative to cardiac patients. Finally, higher frequencies of the IL-10-producing γδ DN T cells were correlated with improved clinical measures of cardiac function in the patients, suggesting a protective role for these cells in Chagas' disease. Taken together, these data show distinct functional characteristics for αβ and γδ DN T cells associated with distinct morbidity rates and clinical forms in human Chagas' disease.
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- 2010
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106. Trypanosoma cruzi-Induced Activation of Functionally Distinct β and CD4–CD8–T Cells in Individuals with Polar Forms of Chagas' Disease
- Author
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Villani, Fernanda Nobre Amaral, da Costa Rocha, Manoel Otávio, Nunes, Maria do Carmo Pereira, Antonelli, Lis Ribeiro do Valle, Magalhães, Luisa Mourão Dias, dos Santos, Janete Soares Coelho, Gollob, Kenneth J., and Dutra, Walderez O.
- Abstract
CD4–CD8–(double-negative [DN]) T cells have recently been shown to display important immunological functions in human diseases. They express or β T-cell receptors that recognize lipid/glycolipid antigens presented via the nonclassical major histocompatibility complex molecules of the CD1 family. We recently demonstrated that while β DN T cells serve primarily to express inflammatory cytokines, DN T cells express mainly interleukin-10 (IL-10) in patients with cutaneous leishmaniasis. We also demonstrated a correlation between DN T cells and the expression of gamma interferon in the acute phase of Trypanosoma cruzi experimental infection. In this work, we sought to investigate whether β or DN T cells display distinct immunoregulatory potentials in patients with polar forms of human Chagas' disease. Our data showed that in vitro infection with T. cruzi leads to expansion of DN T cells in patients with the indeterminate and severe cardiac clinical forms of the disease. However, while β DN T cells primarily produce inflammatory cytokines in both forms of the disease, DN T cells display a marked, significant increase in antigen-specific IL-10 expression in indeterminate patients relative to cardiac patients. Finally, higher frequencies of the IL-10-producing DN T cells were correlated with improved clinical measures of cardiac function in the patients, suggesting a protective role for these cells in Chagas' disease. Taken together, these data show distinct functional characteristics for β and DN T cells associated with distinct morbidity rates and clinical forms in human Chagas' disease.
- Published
- 2010
107. Trypanosoma cruziInfection Induces Differential Modulation of Costimulatory Molecules and Cytokines by Monocytes and T Cells from Patients with Indeterminate and Cardiac Chagas' Disease
- Author
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Souza, Paulo E. A., Rocha, Manoel O. C., Menezes, Cristiane A. S., Coelho, Janete S., Chaves, Andréa C. L., Gollob, Kenneth J., and Dutra, Walderez O.
- Abstract
ABSTRACTInteractions between macrophages and lymphocytes through costimulatory molecules and cytokines are essential for mounting an efficient immune response and controlling its pathogenic potential. Here we demonstrate the immunomodulatory capacity of Trypanosoma cruzi, the causative agent of Chagas' disease, through its ability to induce differential expression of costimulatory molecules and cytokines by monocytes and T cells. Costimulatory molecule and cytokine modulation was evaluated using cells from noninfected individuals and from patients with the asymptomatic indeterminate form and those with the severe cardiac clinical form of Chagas' disease. Our results show that while exposure of monocytes to live T. cruzileads to an increase in the frequency of CD80+monocytes in all groups, it decreases both the frequency and intensity of CD86 expression by monocytes from patients with the cardiac form but not from those with the indeterminate form. Conversely, exposure of lymphocytes to monocytes infected with T. cruziincreased the surface expression of cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) by T cells from indeterminate but not from cardiac patients, compared to that from control patients. These data suggest that T. cruziinduces a potentially down-regulatory environment in indeterminate subjects, which is associated with higher CD80 and CTLA-4 expression. To test the functional importance of this modulation, we evaluated the expression of cytokines after in vitro infection. Although exposure of lymphocytes to parasite-infected monocytes induced high expression of inflammatory and anti-inflammatory cytokines by T cells in all groups, indeterminate patients displayed a higher ratio of monocytes expressing interleukin 10 than tumor necrosis factor alpha following infection than did controls. These data show the ability of T. cruzito actively change the expression of costimulatory molecules and cytokines, suggesting molecular mechanisms for the differential clinical evolution of human Chagas' disease.
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- 2007
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108. Disparate Immunoregulatory Potentials for Double-Negative (CD4– CD8–) α{szligbeta} and γδ T Cells from Human Patients with Cutaneous Leishmaniasis
- Author
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Antonelli, Lis R. V., Dutra, Walderez O., Oliveira, Ricardo R., Torres, Karen C. L., Guimarães, Luiz H., Bacellar, Olivia, and Gollob, Kenneth J.
- Abstract
Although most T lymphocytes express the α{szligbeta} T-cell receptor and either CD4 or CD8 molecules, a small population of cells lacking these coreceptors, CD4– CD8– (double negative [DN]) T cells, has been identified in the peripheral immune system of mice and humans. To better understand the role that this population may have in the human immune response against Leishmania spp., a detailed study defining the activation state, cytokine profile, and the heterogeneity of DN T cells bearing α{szligbeta} or γδ T-cell receptors was performed with a group of well-defined cutaneous leishmaniasis patients. Strikingly, on average 75% of DN T cells from cutaneous leishmaniasis patients expressed the α{szligbeta} T-cell receptor, with the remainder expressing the γδ receptor, while healthy donors displayed the opposite distribution with ∼75% of the DN T cells expressing the γδ T-cell receptor. Additionally, α{szligbeta} DN T cells from cutaneous leishmaniasis patients are compatible with previous antigen exposure and recent activation. Moreover, while α{szligbeta} DN T cells from Leishmania-infected individuals present a proinflammatory cytokine profile, γδ DN T cells express a regulatory profile exemplified by interleukin-10 production. The balance between these subpopulations could allow for the formation of an effective cellular response while limiting its pathogenic potential.
- Published
- 2006
109. Leishmania infantum induces expression of the negative regulatory checkpoint, CTLA‐4, by human naïve CD8+ T cells.
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Viana, Agostinho Gonçalves, Magalhães, Luísa Mourão Dias, Giunchetti, Rodolfo Cordeiro, Dutra, Walderez O., and Gollob, Kenneth J.
- Subjects
T cells ,LEISHMANIA infantum ,CYTOTOXIC T lymphocyte-associated molecule-4 ,VISCERAL leishmaniasis ,LEISHMANIASIS ,INTRACELLULAR pathogens ,INTERLEUKIN-4 ,PROGRAMMED cell death 1 receptors - Abstract
Aims: CD8+ T cells are important in mediating protective responses to intracellular pathogens. However, an uncontrolled response may lead to pathology. The role of CD8+ T cells in different clinical manifestations of human leishmaniasis is controversial and poorly understood. We aim to study the response of CD8+ T cells to the first exposure to different strains of Leishmania, seeking to correlate these findings with clinical manifestations of disease. Methods and results: We have evaluated the expression of granzyme A, inflammatory and anti‐inflammatory cytokines, as well as CTLA‐4 by human naïve CD8+ T cells exposed to Leishmania braziliensis and two different strains of Leishmania infantum in vitro. We observed that while exposure to L braziliensis induced an inflammatory profile, as measured by the expression of granzyme A, IFN‐gamma and IL‐17, as well as a higher IFN/IL‐10 ratio, exposure to L infantum led to a regulatory profile, as measured by lower IFN/IL‐10 ratio and higher expression of CTLA‐4. Conclusion: These results may help explain why patients with the visceral clinical form present a weaker cellular response and, consequently, a worse outcome of the disease. The use of CTLA‐4 checkpoint inhibitors may emerge as a potential immunotherapy to ameliorate the immune response in visceral leishmaniasis patients. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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110. The Role of Co-Stimulatory Molecules in Chagas Disease.
- Author
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Pinto, Bruna F., Medeiros, Nayara I., Fontes-Cal, Tereza C. M., Naziazeno, Isabela M., Correa-Oliveira, Rodrigo, Dutra, Walderez O., and Gomes, Juliana A. S.
- Subjects
CHAGAS' disease ,TRYPANOSOMA cruzi ,MONOCYTES ,LYMPHOCYTES ,T cells - Abstract
Chagas disease, caused by Trypanosoma cruzi, is a potentially life-threatening tropical disease endemic to Latin American countries that affects approximately 8 million people. In the chronic phase of the disease, individuals are classified as belonging to the indeterminate clinical form or to the cardiac and/or digestive forms when clinical symptoms are apparent. The relationship between monocytes and lymphocytes may be an important point to help clarify the complexity that surrounds the clinical symptoms of the chronic phase of Chagas disease. The co-stimulatory signals are essential to determining the magnitude of T cell response to the antigen. The signals are known to determine the regulation of subsequent adaptive immune response. However, little is known about the expression and function of these molecules in Chagas disease. Therefore, this review aims to discuss the possible role of main pathways of co-stimulatory molecule-receptor interactions in this pathology that could be crucial to understand the disease dynamics. [ABSTRACT FROM AUTHOR]
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- 2018
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111. Insights into CD4+ memory T cells following Leishmania infection
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Gollob, Kenneth J., Antonelli, Lis R.V., and Dutra, Walderez O.
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CD4 antigen , *T cells , *LEISHMANIASIS , *MICE , *VACCINES - Abstract
Recent publications by Zaph et al. have highlighted the distinct requirements for generating and maintaining different subpopulations of CD4+ memory T cells after infection with Leishmania major in mice. These studies have advanced the understanding of the nature of long-lasting immunity to Leishmania and, when considered within the context of previous work on both murine and human leishmaniasis, will aid the design of effective vaccines. [Copyright &y& Elsevier]
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- 2005
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112. Cytotoxic CD4 + T cells driven by T-cell intrinsic IL-18R/MyD88 signaling predominantly infiltrate Trypanosoma cruzi -infected hearts.
- Author
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Barbosa CD, Canto FB, Gomes A, Brandao LM, Lima JR, Melo GA, Granato A, Neves EGA, Dutra WO, Oliveira AC, Nóbrega A, and Bellio M
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- Animals, CD4-Positive T-Lymphocytes, Humans, Mice, Myeloid Differentiation Factor 88 genetics, Myeloid Differentiation Factor 88 metabolism, Signal Transduction, Th1 Cells, Chagas Disease, Trypanosoma cruzi
- Abstract
Increasing attention has been directed to cytotoxic CD4
+ T cells (CD4CTLs) in different pathologies, both in humans and mice. The impact of CD4CTLs in immunity and the mechanisms controlling their generation, however, remain poorly understood. Here, we show that CD4CTLs abundantly differentiate during mouse infection with the intracellular parasite Trypanosoma cruzi . CD4CTLs display parallel kinetics to Th1 cells in the spleen, mediate specific cytotoxicity against cells presenting pathogen-derived antigens and express immunoregulatory and/or exhaustion markers. We demonstrate that CD4CTL absolute numbers and activity are severely reduced in both Myd88-/- and Il18ra-/- mice. Of note, the infection of mixed-bone marrow chimeras revealed that wild-type (WT) but not Myd88-/- cells transcribe the CD4CTL gene signature and that Il18ra-/- and Myd88-/- CD4+ T cells phenocopy each other. Moreover, adoptive transfer of WT CD4+ GzB+ T cells to infected Il18ra-/- mice extended their survival. Importantly, cells expressing the CD4CTL phenotype predominate among CD4+ T cells infiltrating the infected mouse cardiac tissue and are increased in the blood of Chagas patients, in which the frequency of CD4CTLs correlates with the severity of cardiomyopathy. Our findings describe CD4CTLs as a major player in immunity to a relevant human pathogen and disclose T-cell intrinsic IL-18R/MyD88 signaling as a key pathway controlling the magnitude of the CD4CTL response., Competing Interests: CB, FC, AG, LB, JL, GM, AG, EN, WD, AO, AN, MB No competing interests declared, (© 2022, Barbosa, Canto, Gomes et al.)- Published
- 2022
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113. Histopathological Characterization of Mitral Valvular Lesions from Patients with Rheumatic Heart Disease.
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Gomes NFA, Pascoal-Xavier MA, Passos LSA, Paula TMN, Aguiar JMS, Guarçoni FV, Nassif MCL, Gelape CL, Braulio R, Costa PHN, Passaglia LG, Martins RB, Dutra WO, and Nunes MCP
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- Adult, Aged, Female, Humans, Male, Middle Aged, Mitral Valve diagnostic imaging, Calcinosis diagnostic imaging, Mitral Valve Insufficiency, Mitral Valve Stenosis diagnostic imaging, Rheumatic Heart Disease diagnostic imaging
- Abstract
Background: The underlying mechanisms by which rheumatic heart disease (RHD) lead to severe valve dysfunction are not completely understood., Objective: The present study evaluated the histopathological changes in mitral valves (MV) seeking an association between the pattern of predominant valvular dysfunction and histopathological findings., Methods: In 40 patients who underwent MV replacement due to RHD, and in 20 controls that underwent heart transplant, histological aspects of the excised MV were analyzed. Clinical and echocardiographic data were also collected. Histological analyses were performed using hematoxylin-eosin staining. Inflammation, fibrosis, neoangiogenesis, calcification and adipose metaplasia were determined. A p value<0.05 was considered to be statistically significant., Results: The mean age of RHD patients was 53±13 years, 36 (90%) were female, whereas the mean age of controls was 50±12 years, similar to the cases, with the majority of males (70%). The rheumatic valve endocardium presented greater thickness than the controls (1.3±0.5 mm versus 0.90±0.4 mm, p=0.003, respectively), and a more intense inflammatory infiltrate in the endocardium (78% versus 36%; p=0.004), with predominance of mononuclear cells. Moderate to marked fibrosis occurred more frequently in rheumatic valves than in control valves (100% vs. 29%; p<0.001). Calcification occurred in 35% of rheumatic valves, especially among stenotic valves, which was associated with the mitral valve area (p=0.003)., Conclusions: Despite intense degree of fibrosis, the inflammatory process remains active in the rheumatic mitral valve, even at late disease with valve dysfunction. Calcification predominated in stenotic valves and in patients with right ventricular dysfunction.
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- 2021
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114. Interleukin-6 gene polymorphism (-174 G/C) is associated with toxoplasmic retinochoroiditis.
- Author
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Cordeiro CA, Moreira PR, Bessa TF, Costa GC, Dutra WO, Campos WR, Oréfice F, Young LH, and Teixeira AL
- Subjects
- Adult, Alleles, Animals, Chorioretinitis metabolism, Chorioretinitis parasitology, Electrophoresis, Polyacrylamide Gel, Female, Follow-Up Studies, Gene Frequency, Genotype, Humans, Interleukin-6 metabolism, Male, Polymerase Chain Reaction, Toxoplasmosis, Ocular metabolism, Toxoplasmosis, Ocular parasitology, Chorioretinitis genetics, DNA genetics, Interleukin-6 genetics, Polymorphism, Genetic, Toxoplasmosis, Ocular genetics
- Abstract
Purpose: Experimental data have demonstrated a relevant role for IL-6 in the modulation of acute ocular toxoplasmosis. Therefore, we aim to investigate the possible association between the IL-6 gene polymorphism at position -174 and toxoplasmic retinochoroiditis (TR) in humans., Methods: Ninety-seven patients with diagnosed TR were recruited from the Uveitis Section, Federal University of Minas Gerais. For comparison, 83 healthy blood donors with positive serology for toxoplasmosis and without retinal signs of previous TR were included in the study. Genomic DNA was obtained from oral swabs of individuals and amplified using polymerase chain reaction (PCR) with specific primers flanking the locus -174 of IL-6 (-174G/C). PCR products were submitted to restriction endonuclease digestion and analysed by polyacrylamide gel electrophoresis to distinguish allele G and C of the IL-6 gene, allowing the detection of the polymorphism and determination of genotypes., Results: There was a significant difference in the genotype (χ(2) = 12.9, p = 0.001) and allele (χ(2) = 6.62, p = 0.01) distribution between TR patients and control subjects. In a subgroup analysis, there was no significant difference in genotypes and allele frequencies regarding TR recurrence., Conclusions: This study suggests that the genotypes related with a lower production of IL-6 may be associated with the occurrence of TR., (© 2013 The Authors. Acta Ophthalmologica © 2013 Acta Ophthalmologica Scandinavica Foundation.)
- Published
- 2013
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115. Trypanosoma cruzi-induced activation of functionally distinct αβ and γδ CD4- CD8- T cells in individuals with polar forms of Chagas' disease.
- Author
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Villani FN, Rocha MO, Nunes Mdo C, Antonelli LR, Magalhães LM, dos Santos JS, Gollob KJ, and Dutra WO
- Subjects
- Adult, Aged, Cross-Sectional Studies, Female, Gene Expression Regulation immunology, Humans, Interleukin-10 genetics, Interleukin-10 metabolism, Male, Middle Aged, Young Adult, Chagas Disease immunology, Receptors, Antigen, T-Cell, alpha-beta immunology, Receptors, Antigen, T-Cell, gamma-delta immunology, Trypanosoma cruzi physiology
- Abstract
CD4(-) CD8(-) (double-negative [DN]) T cells have recently been shown to display important immunological functions in human diseases. They express γδ or αβ T-cell receptors that recognize lipid/glycolipid antigens presented via the nonclassical major histocompatibility complex molecules of the CD1 family. We recently demonstrated that while αβ DN T cells serve primarily to express inflammatory cytokines, γδ DN T cells express mainly interleukin-10 (IL-10) in patients with cutaneous leishmaniasis. We also demonstrated a correlation between DN T cells and the expression of gamma interferon in the acute phase of Trypanosoma cruzi experimental infection. In this work, we sought to investigate whether αβ or γδ DN T cells display distinct immunoregulatory potentials in patients with polar forms of human Chagas' disease. Our data showed that in vitro infection with T. cruzi leads to expansion of DN T cells in patients with the indeterminate and severe cardiac clinical forms of the disease. However, while αβ DN T cells primarily produce inflammatory cytokines in both forms of the disease, γδ DN T cells display a marked, significant increase in antigen-specific IL-10 expression in indeterminate patients relative to cardiac patients. Finally, higher frequencies of the IL-10-producing γδ DN T cells were correlated with improved clinical measures of cardiac function in the patients, suggesting a protective role for these cells in Chagas' disease. Taken together, these data show distinct functional characteristics for αβ and γδ DN T cells associated with distinct morbidity rates and clinical forms in human Chagas' disease.
- Published
- 2010
- Full Text
- View/download PDF
116. Immunoregulatory mechanisms and CD4-CD8- (double negative) T cell subpopulations in human cutaneous leishmaniasis: a balancing act between protection and pathology.
- Author
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Gollob KJ, Antonelli LR, Faria DR, Keesen TS, and Dutra WO
- Subjects
- Animals, Arginase immunology, Forecasting, Humans, Receptors, Antigen, T-Cell, alpha-beta immunology, Receptors, Antigen, T-Cell, gamma-delta immunology, CD4 Antigens drug effects, CD8 Antigens drug effects, Leishmania, Leishmaniasis, Cutaneous immunology, T-Lymphocyte Subsets immunology
- Abstract
Cellular immune responses directed against protozoan parasites are key for controlling pathogen replication and disease resolution. However, an uncontrolled, or improperly controlled, response can be deleterious to the host in terms of both allowing for the establishment of pathology, as well as less effective establishment of memory responses. Human cutaneous leishmaniasis is a disease caused by the infection with Leishmania spp. following a bite from the sandfly, the natural vector of this disease. Tens of millions worldwide are currently infected with Leishmania and no effective vaccines have been developed to date. In the face of the complexity presented by the interaction between a host (humans) with the parasite, Leishmania, and the fact that this parasite is inoculated by another complex, biologically active, vector, the sandfly, it is clearly important to study the immunoregulatory mechanisms that are induced in humans naturally infected by this parasite if we hope to develop effective vaccines and immunotherapeutic treatments in the future. Our laboratory has focused over the years on the study of the local and systemic T cell response during the first episode of cutaneous leishmaniasis suffered by individuals before they undergo antimony treatment. The goal of this review is to briefly outline our findings with hopes of putting our most recent studies concerning the dichotomy between alpha/beta TCR and gamma/delta TCR expressing, CD4-CD8- (double negative-DN) T cells in the context of a balanced immune response against Leishmania and to discuss the implications of these findings toward our understanding of human leishmaniasis.
- Published
- 2008
- Full Text
- View/download PDF
117. Interleukin-10 gene polymorphism (-1082G/A) is associated with toxoplasmic retinochoroiditis.
- Author
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Cordeiro CA, Moreira PR, Andrade MS, Dutra WO, Campos WR, Oréfice F, and Teixeira AL
- Subjects
- Adult, Chorioretinitis parasitology, Electrophoresis, Polyacrylamide Gel, Female, Genotype, Humans, Male, Polymerase Chain Reaction, Chorioretinitis genetics, Interleukin-10 genetics, Polymorphism, Single Nucleotide, Toxoplasmosis, Ocular genetics
- Abstract
Purpose: Experimental data have demonstrated a relevant role for IL-10, an anti-inflammatory cytokine, in the modulation of acute ocular toxoplasmosis. Therefore, this study was conducted to investigate the possible association between an IL10 gene polymorphism at position -1082 and toxoplasmic retinochoroiditis (TR) in humans., Methods: One hundred patients with diagnosed TR were recruited from the Uveitis Section, Federal University of Minas Gerais. For comparison, one hundred healthy blood donors with positive serology for toxoplasmosis and without retinal signs of previous TR were included in the study. Genomic DNA was obtained from oral swabs of individuals and amplified using polymerase chain reaction (PCR) with specific primers flanking the locus -1082 of IL10 (-1082G/A). PCR products were subjected to restriction endonuclease digestion and analyzed by polyacrylamide gel electrophoresis, to distinguish allele G and A of the IL-10 gene, allowing the detection of the polymorphism and determination of genotypes., Results: There was a significant difference in the genotype distribution between TR patients and control subjects (chi(2) = 6.33, P = 0.04). Carriers of the IL10 -1082 A allele (AA+AG genotypes) were more often patients with TR than control subjects (chi(2) = 5.97, P = 0.01, OR, 2.55; 95% CI, 1.11 < OR < 5.55). In a subgroup analysis, there was no significant difference in genotypes and allele carriage regarding visual acuity, involvement of both eyes and TR recurrence., Conclusions: This study suggests that the genotypes related with a low production of IL-10 may be associated with the occurrence of TR.
- Published
- 2008
- Full Text
- View/download PDF
118. Disparate immunoregulatory potentials for double-negative (CD4- CD8-) alpha beta and gamma delta T cells from human patients with cutaneous leishmaniasis.
- Author
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Antonelli LR, Dutra WO, Oliveira RR, Torres KC, Guimarães LH, Bacellar O, and Gollob KJ
- Subjects
- Adolescent, Adult, Aged, Cells, Cultured, Child, Child, Preschool, Cytokines biosynthesis, Female, Humans, Leishmaniasis, Cutaneous metabolism, Leishmaniasis, Cutaneous pathology, Lymphocyte Activation immunology, Male, Middle Aged, T-Lymphocyte Subsets metabolism, T-Lymphocytes metabolism, CD4 Antigens metabolism, CD8 Antigens metabolism, Leishmaniasis, Cutaneous immunology, Receptors, Antigen, T-Cell, alpha-beta metabolism, Receptors, Antigen, T-Cell, gamma-delta metabolism, T-Lymphocyte Subsets immunology, T-Lymphocytes classification, T-Lymphocytes immunology
- Abstract
Although most T lymphocytes express the alphabeta T-cell receptor and either CD4 or CD8 molecules, a small population of cells lacking these coreceptors, CD4- CD8- (double negative [DN]) T cells, has been identified in the peripheral immune system of mice and humans. To better understand the role that this population may have in the human immune response against Leishmania spp., a detailed study defining the activation state, cytokine profile, and the heterogeneity of DN T cells bearing alphabeta or gammadelta T-cell receptors was performed with a group of well-defined cutaneous leishmaniasis patients. Strikingly, on average 75% of DN T cells from cutaneous leishmaniasis patients expressed the alphabeta T-cell receptor, with the remainder expressing the gammadelta receptor, while healthy donors displayed the opposite distribution with approximately 75% of the DN T cells expressing the gammadelta T-cell receptor. Additionally, alphabeta DN T cells from cutaneous leishmaniasis patients are compatible with previous antigen exposure and recent activation. Moreover, while alphabeta DN T cells from Leishmania-infected individuals present a proinflammatory cytokine profile, gammadelta DN T cells express a regulatory profile exemplified by interleukin-10 production. The balance between these subpopulations could allow for the formation of an effective cellular response while limiting its pathogenic potential.
- Published
- 2006
- Full Text
- View/download PDF
119. A functional interleukin-1 beta gene polymorphism is associated with chronic periodontitis in a sample of Brazilian individuals.
- Author
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Moreira PR, de Sá AR, Xavier GM, Costa JE, Gomez RS, Gollob KJ, and Dutra WO
- Subjects
- Adolescent, Adult, Aged, Brazil, Case-Control Studies, Cross-Sectional Studies, Cytosine, Female, Gene Frequency, Humans, Logistic Models, Male, Middle Aged, Odds Ratio, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Surveys and Questionnaires, Thymine, Interleukin-1 genetics, Periodontitis genetics
- Abstract
Background: Interleukin-1 beta (IL-1 beta) is a potent inflammatory mediator and an important polymorphism in the locus +3954 (C/T) of the human IL1 B gene has been shown to affect the levels of this cytokine. This functional polymorphism has been associated with the establishment of inflammatory diseases, including periodontal disease, in European, Asian and North American populations., Objective: The aim of this study was to investigate the association between the IL1 B (+3954) gene polymorphism and the occurrence of different clinical forms of periodontitis in a sample of Brazilian individuals., Methods: This study employed a cross-sectional design involving individuals from the State of Minas Gerais in the south-eastern region of Brazil. Genomic DNA was obtained from oral swabs of 129 individuals and amplified using the polymerase chain reaction (PCR) with specific primers flanking the locus +3954 of IL1 B. PCR products were submitted to restriction endonuclease digestion and analyzed by polyacrylamide gel electrophoresis, to distinguish alleles T and C of the IL1 B gene, allowing for the determination of the genotypes and detection of the polymorphism., Results and Conclusions: The chronic periodontitis group displayed a higher percentage of the T allele (28%) when compared to the aggressive periodontitis group (10.7%, chi(2)=5.24, p=0.02, OR=0.31, CI=0.11--0.88) and to control group (8.7%, chi(2)=7.11, p=0.007, OR=0.24, CI=0.08--0.73). Our data suggested that the polymorphism in the locus +3954 of IL1 B gene could be a risk factor for chronic periodontitis in a sample of Brazilian individuals.
- Published
- 2005
- Full Text
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120. Endogenous IL-4 and IFN-gamma are essential for expression of Th2, but not Th1 cytokine message during the early differentiation of human CD4+ T helper cells.
- Author
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Torres KC, Dutra WO, and Gollob KJ
- Subjects
- Cytokines physiology, Gene Expression Regulation immunology, Humans, T-Lymphocytes, Helper-Inducer immunology, T-Lymphocytes, Helper-Inducer metabolism, Th1 Cells metabolism, Th2 Cells metabolism, Cell Differentiation immunology, Interferon-gamma physiology, Interleukin-4 physiology, Th1 Cells immunology, Th2 Cells immunology
- Abstract
CD4+ T cells can be divided into several distinct effector subpopulations, including Th1 and Th2. Human Th1 cells are essential for the establishment of cellular immune responses, whereas Th2 cells for immunoglobulin E synthesize by B cells and immunoregulation. This study determines the involvement of exogenously and endogenously produced T cell-derived cytokines during early differentiation of naive CD4+ T cells into Th1 and Th2 cells. Cytokine gene expression of purified experienced and naive CD4+T cells in the presence or absence of Th-directing cytokines and neutralizing anti-cytokine antibodies, was determined at early (20 and 40 h) time points, after in vitro activation. These studies demonstrated that: (1) endogenously produced, T cell-derived cytokines (interferon [IFN]-gamma and interleukin [IL]-4), play an important role in the regulation of early gene expression of Th2, but not Th1 type cytokines; (2) Th1-related cytokines, IFN-gamma, and IL-2, are preferentially expressed in cultures directed toward Th1, as compared with Th2; and (3) IL-4 and IFN-gamma showed early message expression in both differentiating populations, indicating a mixed profile of Th1 and Th2 cytokine production in early human Th cell development. These findings point to the critical role for endogenously produced cytokines in the early differentiation of human Th1 or Th2 cells.
- Published
- 2004
- Full Text
- View/download PDF
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