RESUMO
The present work aimed to evaluate the immunogenicity of Leishmania amazonensis iron superoxide dismutase (SOD)-encoding DNA experimental vaccine and the protective properties of this DNA vaccine during infection. The SOD gene was subcloned into the pVAX1 plasmid, and it was used to immunize BALB/c mice. Twenty-one days after the last immunization, mice were sacrificed (immunogenicity studies) or subcutaneously challenged with L. amazonensis (studies of protection), and alterations in cellular and humoral immune responses were evaluated, as well as the course of infection. Mice only immunized with pVAX1-SOD presented increased frequencies of CD4(+) IFN-γ(+), CD8(+)IFN-γ(+) and CD8(+)IL-4(+) lymphocytes; moreover, high levels of IgG2a were detected. After challenge, mice that were immunized with pVAX1-SOD had increased frequencies of the CD4(+)IL-4(+), CD8(+)IFN-γ(+) and CD8(+)IL-4(+) T lymphocytes. In addition, the lymph node cells produced high amounts of IFN-γ and IL-4 cytokines. Increased IgG2a was also detected. The pattern of immunity induced by pVAX1-SOD partially protected the BALB/c mice from a challenge with L. amazonensis, as the animals presented reduced parasitism and lesion size when compared to controls. Taken together, these results indicate that leishmanial SOD modulates the lymphocyte response, and that the elevation in IFN-γ possibly accounted for the decreased skin parasitism observed in immunized animals.
Assuntos
Leishmania mexicana/imunologia , Vacinas contra Leishmaniose/imunologia , Leishmaniose/imunologia , Vacinas de DNA/imunologia , Animais , Citocinas/imunologia , Imunização , Imunoglobulina G/imunologia , Interferon gama/imunologia , Interleucina-4/imunologia , Leishmaniose/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Superóxido Dismutase/genética , Subpopulações de Linfócitos T/imunologiaRESUMO
Regulatory T (TREG) cells play an important role in maintaining immune tolerance and avoiding autoimmunity. We analyzed the expression of membrane molecules in TREG and effector T cells in systemic lupus erythematosus (SLE). TREG and effector T cells were analyzed for the expression of CTLA-4, PD1, CD28, CD95, GITR, HLA-DR, OX40, CD40L, and CD45RO in 26 patients with active disease, 31 with inactive disease, and 26 healthy controls. TREG cells were defined as CD25+/high CD127 Ø/low FoxP3+, and effector T cells were defined as CD25+CD127+FoxP3 Ø. The ratio of TREG to effector T cells expressing GITR, PD1, HLA-DR, OX40, CD40L, and CD45RO was determined in the three groups. The frequency of TREG cells was similar in patients with SLE and controls. However, SLE patients had a decreased frequency of CTLA-4+TREG and CD28+TREG cells and an increased frequency of CD40L+TREG cells. There was a decrease in the TREG/effector-T ratio for GITR+, HLA-DR+, OX40+, and CD45RO+ cells, and an increased ratio of TREG/effector-T CD40L+ cells in patients with SLE. In addition, CD40L+TREG cell frequency correlated with the SLE disease activity index (P=0.0163). In conclusion, our findings showed several abnormalities in the expression of functionally critical surface molecules in TREG and effector T cells in SLE that may be relevant to the pathogenesis of this disease.
Assuntos
Antígenos de Superfície/metabolismo , Leucócitos Mononucleares/metabolismo , Lúpus Eritematoso Sistêmico/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Análise de Variância , Antígenos CD28/análise , Ligante de CD40/análise , Antígeno CTLA-4/análise , Feminino , Citometria de Fluxo , Fatores de Transcrição Forkhead/análise , Proteína Relacionada a TNFR Induzida por Glucocorticoide/análise , Antígenos HLA-DR/análise , Humanos , Subunidade alfa de Receptor de Interleucina-2/análise , Subunidade alfa de Receptor de Interleucina-7/análise , Antígenos Comuns de Leucócito/análise , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/análise , Receptores OX40/análise , Estatísticas não Paramétricas , Receptor fas/análiseRESUMO
Regulatory T (TREG) cells play an important role in maintaining immune tolerance and avoiding autoimmunity. We analyzed the expression of membrane molecules in TREG and effector T cells in systemic lupus erythematosus (SLE). TREG and effector T cells were analyzed for the expression of CTLA-4, PD1, CD28, CD95, GITR, HLA-DR, OX40, CD40L, and CD45RO in 26 patients with active disease, 31 with inactive disease, and 26 healthy controls. TREG cells were defined as CD25+/highCD127Ø/lowFoxP3+, and effector T cells were defined as CD25+CD127+FoxP3Ø. The ratio of TREG to effector T cells expressing GITR, PD1, HLA-DR, OX40, CD40L, and CD45RO was determined in the three groups. The frequency of TREG cells was similar in patients with SLE and controls. However, SLE patients had a decreased frequency of CTLA-4+TREG and CD28+TREG cells and an increased frequency of CD40L+TREG cells. There was a decrease in the TREG/effector-T ratio for GITR+, HLA-DR+, OX40+, and CD45RO+ cells, and an increased ratio of TREG/effector-T CD40L+ cells in patients with SLE. In addition, CD40L+TREG cell frequency correlated with the SLE disease activity index (P=0.0163). In conclusion, our findings showed several abnormalities in the expression of functionally critical surface molecules in TREG and effector T cells in SLE that may be relevant to the pathogenesis of this disease.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antígenos de Superfície/metabolismo , Leucócitos Mononucleares/metabolismo , Lúpus Eritematoso Sistêmico/imunologia , Linfócitos T Reguladores/imunologia , Análise de Variância , /análise , /análise , /análise , /análise , /análise , Citometria de Fluxo , Fatores de Transcrição Forkhead/análise , Proteína Relacionada a TNFR Induzida por Glucocorticoide/análise , Antígenos HLA-DR/análise , /análise , /análise , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/fisiopatologia , Receptor de Morte Celular Programada 1/análise , /análise , Estatísticas não ParamétricasRESUMO
UNLABELLED: The etiology of endometriosis remains poorly understood but circulating stem cells may contribute. Telomeres shorten with cell divisions and age. Stem cells attempt to compensate for telomere attrition through the action of telomerase. Since circulating stem cells may contribute to endometriosis, we compared telomere content in lymphocytes of patients with and without endometriosis. METHODS: Observational study comparing peripheral lymphocytes telomere content, measured by quantitative polymerase chain reaction, in patients with (n = 86) and without endometriosis (n = 21). FINDINGS: Patients with endometriosis had longer telomeres than that of matched, endometriosis-free controls (telomere to single copy gene ratio [T/S ratio] of 1.62 vs 1.34, respectively, P = .00002). Patients with endometriosis were 8.1-fold more likely to have long telomeres. (odds ratio = 8.1, 95% confidence interval: 1.28-51.57, P = .0264). INTERPRETATION: Longer telomeres could be consistent with a stem cell origin of endometriosis.
Assuntos
Endometriose/genética , Linfócitos/metabolismo , Homeostase do Telômero , Telômero/genética , Adulto , Estudos de Casos e Controles , Endometriose/sangue , Endometriose/diagnóstico , Feminino , Marcadores Genéticos , Humanos , Reação em Cadeia da Polimerase , Telômero/metabolismoRESUMO
The host immune response, including innate and adaptive immunity, plays a critical role in determining the outcome of viral infection. Nevertheless, little is known about the exact reasons for the failure of the host immune system in controlling hepatitis C virus (HCV) infection. Impairment of dendritic cells (DCs) function is probably one of the mechanisms responsible for immune evasion of HCV. In this study, the frequency and phenotype of DCs subsets were analyzed in three groups: HCV-infected individuals who developed viral persistence (1), HCV-infected individuals who spontaneously cleared the virus (2) and HCV-seronegative uninfected subjects (3). The results showed that the frequency of DCs subsets was not statistically significant between groups. Plasmacytoid DCs circulating exhibited an immature phenotype characterized by low expression of CD86. On the other hand, CD86 expression in myeloid DCs was significantly higher in chronic infected individuals compared to healthy controls (P=0.037). A positive correlation was observed between CD86(+) myeloid DC (mDC) and HCV viral load (r=0.4121, P=0.0263). These results suggest that HCV did not have an inhibitory effect on mDC maturation and the HCV viremia drives the increase of CD86 expression in mDC. The regulation of DCs maturation and migration lies at the level of intracellular signaling. HCV can activate or block intracellular signaling pathways and alter DC function. In conclusion, the present study suggests that imbalance of DC maturation by the virus represents a mechanism of evasion of the immune system despite the fact that HCV viremia appears to exert a "stimulatory" effect on cell-surface immune phenotype.
Assuntos
Antígeno B7-2/biossíntese , Células Dendríticas/imunologia , Hepacivirus/imunologia , Hepatite C/imunologia , Viremia/imunologia , Adulto , Feminino , Voluntários Saudáveis , Hepatite C/virologia , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Carga ViralRESUMO
Endometriosis is a chronic benign disease that affects women of reproductive age causing abdominal pain and infertility. Its pathogenesis remains obscure despite all the research conducted over the past 100 years. However, there is a consensus among the specialists that the basis of its pathophysiology would be multifactorial. Many publications have demonstrated that chemokines are somehow associated with the development of endometriosis and infertility. In this study, we reviewed all PubMed literature using MeSH terms "chemokines" and "endometriosis" as well as "chemokines" and "female infertility" to establish what we know and what we do not yet know about this relationship.
Assuntos
Quimiocinas/imunologia , Endometriose/imunologia , Infertilidade Feminina/imunologia , Animais , Feminino , HumanosRESUMO
A new subtype of CD4+ T lymphocytes characterized by the production of interleukin 17, i.e., TH17 cells, has been recently described. This novel T cell subset is distinct from type 1 and type 2 T helper cells. The major feature of this subpopulation is to generate significant amounts of pro-inflammatory cytokines, therefore appearing to be critically involved in protection against infection caused by extracellular microorganisms, and in the pathogenesis of autoimmune diseases and allergy. The dynamic balance among subsets of T cells is important for the modulation of several steps of the immune response. Disturbances in this balance may cause a shift from normal immunologic physiology to the development of immune-mediated disorders. In autoimmune diseases, the fine balance between the proportion and degree of activation of the various T lymphocyte subsets can contribute to persistent undesirable inflammatory responses and tissue replacement by fibrosis. This review highlights the importance of TH17 cells in this process by providing an update on the biology of these cells and focusing on their biology and differentiation processes in the context of immune-mediated chronic inflammatory diseases.
Assuntos
Animais , Humanos , Camundongos , Doenças Autoimunes/imunologia , /imunologia , /biossíntese , Subpopulações de Linfócitos T/imunologia , Modelos Animais de Doenças , Subpopulações de Linfócitos TRESUMO
A new subtype of CD4+ T lymphocytes characterized by the production of interleukin 17, i.e., TH17 cells, has been recently described. This novel T cell subset is distinct from type 1 and type 2 T helper cells. The major feature of this subpopulation is to generate significant amounts of pro-inflammatory cytokines, therefore appearing to be critically involved in protection against infection caused by extracellular microorganisms, and in the pathogenesis of autoimmune diseases and allergy. The dynamic balance among subsets of T cells is important for the modulation of several steps of the immune response. Disturbances in this balance may cause a shift from normal immunologic physiology to the development of immune-mediated disorders. In autoimmune diseases, the fine balance between the proportion and degree of activation of the various T lymphocyte subsets can contribute to persistent undesirable inflammatory responses and tissue replacement by fibrosis. This review highlights the importance of TH17 cells in this process by providing an update on the biology of these cells and focusing on their biology and differentiation processes in the context of immune-mediated chronic inflammatory diseases.
Assuntos
Doenças Autoimunes/imunologia , Linfócitos T CD4-Positivos/imunologia , Interleucina-17/biossíntese , Subpopulações de Linfócitos T/imunologia , Animais , Linfócitos T CD4-Positivos/metabolismo , Modelos Animais de Doenças , Humanos , Camundongos , Subpopulações de Linfócitos T/metabolismoRESUMO
The immune consequences of in utero HIV exposure to uninfected children whose mothers were submitted to highly active antiretroviral therapy (HAART) during gestation are not well defined. We evaluated 45 HIV-exposed uninfected (ENI) neonates and 45 healthy unexposed control (CT) neonates. All HIV-infected mothers received HAART during pregnancy, and the viral load at delivery was <50 copies/mL for 56.8%. Twenty-three ENI neonates were further evaluated after 12 months and compared to 23 unexposed healthy age-matched infants. Immunophenotyping was performed by flow cytometry in cord and peripheral blood. Cord blood lymphocyte numbers did not differ between groups. However, ENI neonates had a lower percentage of naive T cells than CT neonates (CD4+, 76.6 vs 83.1%, P < 0.001; CD8+, 70.9 vs 79.6%, P = 0.003) and higher percentages of central memory T cells than CT neonates (CD4+, 13.9 vs 8.7%, P < 0.001; CD8+, 8.6 vs 4.8%, P = 0.001). CD38 mean fluorescence intensity of T cells was higher in ENI neonates (CD4+, 62.2 vs 52.1, P = 0.007; CD8+, 47.7 vs 35.3, P < 0.001). At 12 months, ENI infants still had higher mean fluorescence intensity of CD38 on T cells (CD4+, 34.2 vs 23.3, P < 0.001; CD8+, 26.8 vs 19.4, P = 0.035). Despite effective maternal virologic control at delivery, HIV-exposed uninfected children were born with lower levels of naive T cells. Immune activation was present at birth and remained until at least 12 months of age, suggesting that in utero exposure to HIV causes subtle immune abnormalities.
Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , HIV-1/imunologia , Memória Imunológica/imunologia , Linfócitos T/imunologia , Adolescente , Adulto , Contagem de Células Sanguíneas , Estudos de Casos e Controles , Feminino , Sangue Fetal , Citometria de Fluxo , Infecções por HIV/prevenção & controle , Humanos , Memória Imunológica/efeitos dos fármacos , Imunofenotipagem , Lactente , Ativação Linfocitária/imunologia , Masculino , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/imunologia , Carga Viral , Adulto JovemRESUMO
The immune consequences of in utero HIV exposure to uninfected children whose mothers were submitted to highly active antiretroviral therapy (HAART) during gestation are not well defined. We evaluated 45 HIV-exposed uninfected (ENI) neonates and 45 healthy unexposed control (CT) neonates. All HIV-infected mothers received HAART during pregnancy, and the viral load at delivery was <50 copies/mL for 56.8 percent. Twenty-three ENI neonates were further evaluated after 12 months and compared to 23 unexposed healthy age-matched infants. Immunophenotyping was performed by flow cytometry in cord and peripheral blood. Cord blood lymphocyte numbers did not differ between groups. However, ENI neonates had a lower percentage of naive T cells than CT neonates (CD4+, 76.6 vs 83.1 percent, P < 0.001; CD8+, 70.9 vs 79.6 percent, P = 0.003) and higher percentages of central memory T cells than CT neonates (CD4+, 13.9 vs 8.7 percent, P < 0.001; CD8+, 8.6 vs 4.8 percent, P = 0.001). CD38 mean fluorescence intensity of T cells was higher in ENI neonates (CD4+, 62.2 vs 52.1, P = 0.007; CD8+, 47.7 vs 35.3, P < 0.001). At 12 months, ENI infants still had higher mean fluorescence intensity of CD38 on T cells (CD4+, 34.2 vs 23.3, P < 0.001; CD8+, 26.8 vs 19.4, P = 0.035). Despite effective maternal virologic control at delivery, HIV-exposed uninfected children were born with lower levels of naive T cells. Immune activation was present at birth and remained until at least 12 months of age, suggesting that in utero exposure to HIV causes subtle immune abnormalities.
Assuntos
Adolescente , Adulto , Feminino , Humanos , Lactente , Masculino , Gravidez , Adulto Jovem , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , HIV-1 , Memória Imunológica/imunologia , Linfócitos T/imunologia , Contagem de Células Sanguíneas , Estudos de Casos e Controles , Sangue Fetal , Citometria de Fluxo , Infecções por HIV/prevenção & controle , Imunofenotipagem , Memória Imunológica/efeitos dos fármacos , Ativação Linfocitária/imunologia , Complicações Infecciosas na Gravidez/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/imunologia , Carga Viral , Adulto JovemRESUMO
Glycolipoprotein (GLP) from pathogenic serovars of Leptospira has been implicated in the pathogenesis of leptospirosis by its presence in tissues of experimental animals with leptospirosis, the inhibition of the Na,K-ATPase pump activity, and induced production of cytokines. The aims of the present study were to investigate the induction of IL-6 by GLP in peripheral blood mononuclear cells (PBMC) and to demonstrate monocyte stimulation at the cellular level in whole blood from healthy volunteers. PBMC were stimulated with increasing concentrations (5 to 2500 ng/ml) of GLP extracted from the pathogenic L. interrogans serovar Copenhageni, lipopolysaccharide (positive control) or medium (negative control), and supernatants were collected after 6, 20/24, and 48 h, and kept at -80 degrees C until use. Whole blood was diluted 1:1 in RPMI medium and cultivated for 6 h, with medium, GLP and lipopolysaccharide as described above. Monensin was added after the first hour of culture. Supernatant cytokine levels from PBMC were measured by ELISA and intracellular IL-6 was detected in monocytes in whole blood cultures by flow-cytometry. Monocytes were identified in whole blood on the basis of forward versus side scatter parameters and positive reactions with CD45 and CD14 antibodies. GLP ( > or = 50 ng/ml)-induced IL-6 levels in supernatants were detected after 6-h incubation, reaching a peak after 20/24 h. The percentage of monocytes staining for IL-6 increased with increasing GLP concentration. Thus, our findings show a GLP-induced cellular activation by demonstrating the ability of GLP to induce IL-6 and the occurrence of monocyte activation in whole blood at the cellular level.
Assuntos
Glicoproteínas/farmacologia , Interleucina-6/biossíntese , Leptospira interrogans/imunologia , Monócitos/imunologia , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Interleucina-6/imunologia , Antígenos Comuns de Leucócito/imunologia , Receptores de Lipopolissacarídeos/imunologia , Monócitos/microbiologiaRESUMO
Tuberculosis (TB) is usually more severe in HIV-infected patients, and the immune derangement found in co-infected patients may differ from that in each isolated disease. Following mitogen stimulation of peripheral blood mononuclear cells (PBMC), interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha production was evaluated in T cells by flow cytometry, and in culture supernatants by enzyme-linked immunosorbent assay (ELISA) in 33 individuals: 11 AIDS patients with tuberculosis, six asymptomatic HIV-1-infected patients, eight patients with tuberculosis and eight healthy controls. The proportion of CD4+ T lymphocytes expressing IFN-gamma did not differ between the groups, whereas a trend towards increased proportions of TNF-alpha-expression in CD4+ T cells was observed in the TB compared to the HIV group, while intermediate values were observed in co-infected patients. Detection of IFN-gamma and TNF-alpha in CD8+ T lymphocytes was higher in TB than in HIV individuals. Co-infected patients presented intermediate values for IFN-gamma, while TNF-alpha detection was similar to that in HIV mono-infection. In conclusion, the proportion of T cells expressing IFN-gamma was relatively preserved in co-infected patients compared to TB patients, while the percentage of T cells expressing TNF-alpha was decreased, mainly in CD8+ T lymphocytes. However, the marked reduction in T lymphocyte numbers in co-infected patients led to a striking reduction of both cytokines in PBMC supernatants, a finding that is consistent with the impaired response to Mycobacterium tuberculosis.
Assuntos
Infecções por HIV/imunologia , Interferon gama/biossíntese , Linfócitos T/imunologia , Tuberculose/imunologia , Fator de Necrose Tumoral alfa/biossíntese , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Síndrome da Imunodeficiência Adquirida/imunologia , Adulto , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Células Cultivadas , Feminino , HIV-1/imunologia , Humanos , Interferon gama/imunologia , Leucócitos Mononucleares/imunologia , Contagem de Linfócitos/métodos , Masculino , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Glycolipoprotein (GLP) from pathogenic serovars of Leptospira has been implicated in the pathogenesis of leptospirosis by its presence in tissues of experimental animals with leptospirosis, the inhibition of the Na,K-ATPase pump activity, and induced production of cytokines. The aims of the present study were to investigate the induction of IL-6 by GLP in peripheral blood mononuclear cells (PBMC) and to demonstrate monocyte stimulation at the cellular level in whole blood from healthy volunteers. PBMC were stimulated with increasing concentrations (5 to 2500 ng/ml) of GLP extracted from the pathogenic L. interrogans serovar Copenhageni, lipopolysaccharide (positive control) or medium (negative control), and supernatants were collected after 6, 20/24, and 48 h, and kept at -80°C until use. Whole blood was diluted 1:1 in RPMI medium and cultivated for 6 h, with medium, GLP and lipopolysaccharide as described above. Monensin was added after the first hour of culture. Supernatant cytokine levels from PBMC were measured by ELISA and intracellular IL-6 was detected in monocytes in whole blood cultures by flow-cytometry. Monocytes were identified in whole blood on the basis of forward versus side scatter parameters and positive reactions with CD45 and CD14 antibodies. GLP ( > or = 50 ng/ml)-induced IL-6 levels in supernatants were detected after 6-h incubation, reaching a peak after 20/24 h. The percentage of monocytes staining for IL-6 increased with increasing GLP concentration. Thus, our findings show a GLP-induced cellular activation by demonstrating the ability of GLP to induce IL-6 and the occurrence of monocyte activation in whole blood at the cellular level.
Assuntos
Humanos , Glicoproteínas/farmacologia , /biossíntese , Leptospira interrogans/imunologia , Monócitos/imunologia , /imunologia , /imunologia , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , /imunologia , Monócitos/microbiologiaRESUMO
In this report we evaluated CD4(+) T, CD8(+) T and natural killer (NK) cell counts, the levels of naive/memory subsets within the CD4(+) T lymphocyte population, expression of CD38 on T lymphocytes, and CD4(+) and CD8(+) T cell cytokine production in two girls with hyper-IgM (HIM) syndrome. Both girls developed recurrent infections early in infancy, presenting a wide spectrum of clinical manifestations, with a strikingly different disease severity between them. CD4(+) T cell counts were low in both children (patient 1: 214 cells/mm(3) and patient 2: 392 cells/mm(3)), and the CD4/CD8 T cell ratio was 0.4 for patient 1, the patient with the more severe disease, and 1.4 for patient 2. NK cell numbers were low in patient 1 (60 cells/mm(3)) and borderline (286 cells/mm(3)) with regard to normal levels in patient 2. An imbalance of naive and memory/effector cell subsets was found in both girls, with the percentage of CD45RA(+) 27(+) (naive) CD4(+) T lymphocytes being 5.8 and 12.4 for patients 1 and 2, respectively. Expression of CD38 on the surface of T lymphocytes was low in patient 1. Detection of intracellular interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha in CD4(+) and CD8(+) T lymphocytes upon PMA-Io stimulus was preserved in both children. In conclusion, we found low numbers of CD4(+) T lymphocytes and a dramatic redistribution of naive and memory/effector CD4(+) T lymphocytes in two girls with non-X-linked HIM syndrome. Furthermore, we found low expression of CD38 on T lymphocytes and low numbers of NK cells in the patient with the more severe disease, indicating a possible role for these cells in the pathogenesis of this immunodeficiency.
Assuntos
ADP-Ribosil Ciclase/análise , Antígenos CD/análise , Citocinas/imunologia , Imunoglobulina M/imunologia , Síndromes de Imunodeficiência/imunologia , Subpopulações de Linfócitos T/imunologia , ADP-Ribosil Ciclase 1 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Pré-Escolar , Citocinas/análise , Feminino , Citometria de Fluxo , Humanos , Memória Imunológica , Imunofenotipagem/métodos , Lactente , Interferon gama/análise , Líquido Intracelular/química , Células Matadoras Naturais/imunologia , Contagem de Linfócitos , Glicoproteínas de Membrana , Fator de Necrose Tumoral alfa/análiseRESUMO
Allogeneic bone marrow transplantation (ALLOBMT) is associated with an increased risk of cytomegalovirus (CMV) morbidity compared to autologous BMT (AUTOBMT). To investigate this, we evaluated AUTOBMT and ALLOBMT patients regarding anti-CMV immune reconstitution at 1 and 4 months after BMT and on the day after first CMV antigenemia detection. Intermittent ganciclovir preemptive therapy was prompted by antigenemia of >or=2 cells. One month after transplant, AUTOBMT recipients already displayed larger CD8+ T cell numbers than ALLOBMT recipients, but comparably small CD4+ T cell numbers. Most AUTOBMT patients had positive CMV antigen (CMV-Ag)-induced lymphoproliferation (86%) and IFN-gamma secretion (86%), whereas this was infrequently seen in ALLOBMT patients (20 and 10%, respectively). This early AUTOBMT immune reconstitution was associated with a lower frequency of CMV reactivation up to +4 months in AUTOBMT (21%) than ALLOBMT patients (91%). At +4 months, most ALLOBMT recipients had also recovered CMV-Ag immune responses. At first antigenemia detection, all 3 AUTOBMT recipients already displayed anti-CMV immune functions and 2 cleared the infection without therapy, whereas of the 10 ALLOBMT recipients only 1 had positive lymphoproliferation. In the latter group, none had IFN-gamma secretion or cleared the infection without therapy. Thus, differences in anti-CMV immune reconstitution may help to explain the contrasting rates of CMV morbidity between ALLOBMT and AUTOBMT patients.
Assuntos
Transplante de Medula Óssea/imunologia , Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Interferon gama/biossíntese , Ativação Linfocitária , Transplante Autólogo/imunologia , Transplante Homólogo/imunologia , Viremia/imunologia , Adolescente , Adulto , Antígenos Virais/sangue , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Citomegalovirus/crescimento & desenvolvimento , Feminino , Doença Enxerto-Hospedeiro , Humanos , Imunocompetência , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Neoplasias/terapia , Condicionamento Pré-Transplante , Ativação ViralRESUMO
The cellular immune response probably plays a pivotal role in determining the clinical outcome after exposure to Mycobacterium tuberculosis. We used multi-parameter flow-cytometry to evaluate the distribution of T-lymphocyte subsets during infection and disease caused by M. tuberculosis. Samples were obtained from 71 volunteers to identify the T CD4+ and CD8+ lymphocyte numbers, and the activation plus memory/naïve phenotypes, as defined by CD38, HLA-DR, CD45RA and CD27 markers. Subjects were divided into 18 healthy volunteers without detectable reaction to purified protein derivative (PPD-), 18 health care workers with a recent conversion to PPD, 20 patients with active pulmonary tuberculosis (TBC) and 15 patients with treated TBC at 6 months of therapy. By multiple-comparison analyses, the T CD4+ lymphocyte number of the TBC group was lower than the PPD- group (P < 0.05). This difference was apparently lost after treatment. The higher and the lower number of naïve T CD4+ cells was observed in the PPD- and TBC group, respectively. CD8+ T lymphocytes were also statistically different among the four groups (P = 0.0002), lower in the TBC group (P < 0.05). CD8+ T lymphocyte activation was evaluated by the CD38 and HLA-DR surface expression. The percentage distribution of these markers was statistically different between the four groups (P = 0.0055). TBC patients had a higher percentage of CD38+ cells and mean fluorescence index, suggesting an overall increase of cell activation. These results suggest that peripheral T lymphocytes reflect cellular activation during TBC, along with possible redistribution of naïve, memory/effector and late differentiated memory/effector phenotypes in the peripheral blood after infection and disease caused by M. tuberculosis.
Assuntos
Antígenos CD , Mycobacterium tuberculosis , Subpopulações de Linfócitos T/imunologia , Tuberculose Pulmonar/imunologia , ADP-Ribosil Ciclase , ADP-Ribosil Ciclase 1 , Adolescente , Adulto , Antígenos de Diferenciação/análise , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Citometria de Fluxo , Antígenos HLA-DR/análise , Humanos , Memória Imunológica , Imunofenotipagem , Antígenos Comuns de Leucócito/análise , Ativação Linfocitária , Contagem de Linfócitos , Masculino , Glicoproteínas de Membrana , Pessoa de Meia-Idade , NAD+ Nucleosidase/análise , Subpopulações de Linfócitos T/classificação , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/análiseRESUMO
This study was designed to investigate the oral yeast colonization rate of household contacts of AIDS patients. Sixty-four AIDS household contacts were sequentially enrolled along with 103 HIV-negative blood bank donors (control group). Samples were obtained by swabbing the oral mucosa. Yeast isolates were identified by classical methods and antifungal susceptibility testing was performed according to NCCLS microbroth assay. Candida spp. was recovered from the oral cavity of 33% of the AIDS household contacts, in contrast with 14% of the control group (P = 0.003 or P = 0.04 after adjusting for oral prosthesis use). Candida albicans was the most frequently isolated species in both groups. All of the isolates were susceptible to fluconazole, itraconazole and ketoconazole. In conclusion, we were able to demonstrate a higher colonization rate in the AIDS household contacts group compared with the control group. No resistant isolates to antifungal drugs was observed. We suggest that the contact with AIDS patients may play a role as a risk factor for developing oral colonization by Candida spp.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/transmissão , Candidíase Bucal/transmissão , Saúde da Família , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Antifúngicos/uso terapêutico , Azóis/uso terapêutico , Candida albicans , Candidíase Bucal/epidemiologia , Candidíase Bucal/microbiologia , Portador Sadio/epidemiologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Mucosa Bucal/microbiologia , Prevalência , Estudos Prospectivos , Fatores de RiscoRESUMO
Hepatitis C virus (HCV) causes infectious hepatitis worldwide. It is transmitted mainly by blood products and sharing of intravenous paraphernalia during illicit drug use. High prevalence rates have been described among specific groups considered to be at higher risk for HCV infection, including prison inmates. The objectives of this study were: to determine the HCV seroprevalence among inmates of Casa de Detenção de São Paulo; to identify risk factors for HCV infection; and to compare the seroprevalence of HCV to other blood borne or sexually transmitted diseases. From December, 1993, to January, 1994, a total of 779 inmates were interviewed to collect information on sociodemographic status, sexual behavior, and past experience with illicit drugs. Blood samples were obtained from 756 inmates for serological tests. 310 (41%) blood samples were positive for anti-HCV, 425 (56.2%) were negative, and 21 (2.8%) showed indeterminate results. In this population, we found a seroprevalence of 13.7% for HIV, 3.3% for syphilis (VDRL), and 68.1% for hepatitis B virus previous infection. Four variables were each identified as associated with a positive anti-HCV serologic test: a positive VDRL (OR = 2.63 IC 95% 1.08 to 6.36); a time of current imprisonment longer than 130 months (OR = 2.44 IC 95% 1.04 to 5.71); previous incarceration at Casa de Detenção de São Paulo (OR = 1.73 IC 95% 1.19 to 2.52) and; illicit drug use before admission to the Casa de Detenção de São Paulo (OR = 1.64 IC 95% 1.15 to 2.33). The seroprevalence of HCV antibodies among the study population was high (41%), indeed, one of the highest clusters of HCV infection recorded until now. Four variables were each shown to be associated with HCV infection. The simultaneous presence of these 4 variables is associated with an 82% probability of being anti-HCV positive. Although risk factor analysis indicates most HCV infections occur prior to inprisonment, initiation of control measures to prevent continued transmission after incarceration should be done.
Assuntos
Hepatite C/epidemiologia , Prisioneiros , Adulto , Brasil/epidemiologia , Estudos Transversais , Hepatite C/imunologia , Hepatite C/transmissão , Anticorpos Anti-Hepatite C/sangue , Humanos , Masculino , Prevalência , Estudos Retrospectivos , Fatores de Risco , Estudos Soroepidemiológicos , Doenças Virais Sexualmente Transmissíveis/epidemiologia , Doenças Virais Sexualmente Transmissíveis/transmissão , Doenças Virais Sexualmente Transmissíveis/virologia , Transtornos Relacionados ao Uso de Substâncias/complicaçõesRESUMO
The outcome of patients with sepsis arises from multiple factors affecting both the host and the invading microorganisms. Age, presence of underlying disease, source of infection and some specific etiological agents have been related to prognosis. Appropriateness of antimicrobial therapy, considering the in vitro susceptibility tests for the infecting bacteria, has been strongly associated with the outcome. Therefore even after the cascade of sepsis has been triggered, the control of bacteria growth is still fundamental for the outcome of the infection. This is a major distinction point from experimental studies in which whole killed bacteria and their products are used as model of sepsis. However, even within the setting of adequate antimicrobial use, patients still die of sepsis. Thus, strategies focusing on further therapy targets are an important area of interest for basic and clinical research. Although such adjunctive sepsis therapy has failed to achieve consistent better survival rates so far, nevertheless, it improved our understanding of the pathophysiological events seen in sepsis that the possibility that a new and effective treatment may arise has been warmly considered. In this paper we aim to review some aspects of the pathogenesis of sepsis, focusing on recent advances and on possible targets for adjunctive therapy. Published clinical trials and experimental data supporting such trials are commented on.