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1.
Nephrology (Carlton) ; 25(8): 599-606, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32147900

RESUMO

AIM: This study aimed to investigate the current progression status from screening phase to further investigation phase in the Japanese school urine mass screening (SUS) project. METHODS: This retrospective cohort study on the SUS project across the Shiga Prefecture during 2012 to 2017 analysed data from school life instruction sheets, which are principal documents in the SUS project, regarding urinalysis, attendance at follow-up and diagnoses. RESULTS: Between the years 2012 to 2017, a median of 107 out of 83 749 elementary school students (aged 6-11 years) and 215 out of 42 870 junior high students (aged 12-14 years) had urine abnormalities identified for the first time in the SUS project. Among those with urine abnormalities, a mean of 4.2% of elementary school and 1.8% of junior high school students, respectively, were diagnosed with suspected glomerulonephritis for the first time. Overall, 5.9% (95% confidence interval [CI] 4.1, 7.7) and 23.6% (95% CI 21.3, 25.9) of proteinuria-positive elementary and junior high school students, respectively, did not undergo further investigations. The probability of a student undergoing further investigations was not affected by the local availability of medical care benefits. CONCLUSION: In the current SUS project, screening frequently does not lead to further investigation, especially among junior high school students. To maintain the integrity of the SUS project and to prevent the progression of renal disease in young students, efforts including elucidation of barriers to further investigations should be made to reduce the proportions of students not undergoing further investigations for abnormal urinalysis findings.

2.
Intern Med ; 59(1): 93-99, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31902910

RESUMO

Atypical hemolytic uremic syndrome (aHUS) is an extremely rare condition caused by an excessive activation of the complement pathway based on genetic or acquired dysfunctions in complement regulation, leading to thrombotic microangiopathy (TMA). A complement-amplifying condition (CAC) can trigger aHUS occurrence along with complement abnormality. We herein report a case of severe TMA after laparoscopic myomectomy in a healthy woman. This case was eventually diagnosed as complement-mediated TMA secondary to surgical invasive stress as a CAC, with no definitive diagnosis of aHUS despite a genetic test. The patient fully recovered after several eculizumab administrations.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Laparoscopia/efeitos adversos , Hemorragia Pós-Operatória/complicações , Microangiopatias Trombóticas/tratamento farmacológico , Miomectomia Uterina/efeitos adversos , Adulto , Inativadores do Complemento/uso terapêutico , Feminino , Humanos , Doenças Raras , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/etiologia
3.
J Hum Genet ; 63(6): 755-759, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29556035

RESUMO

Pathogenic variants in specific complement-related genes lead to atypical hemolytic uremic syndrome (aHUS). Some reports have indicated that patients with digenic variants in these genes might present severer phenotypes. Upon detecting novel intronic variants, transcriptional analysis is necessary to prove pathogenicity; however, when intronic variants are located in intron 1 and, as a result, no transcript is produced, no appropriate method had been established to reveal the pathogenicity. Recently, the minigene assay was used to assess the pathogenicity of intronic variants. Here, we report an infantile case of aHUS caused by digenic mutations in two different complement-related genes, C3 and MCP. Targeted sequencing detected a known variant in C3 and a novel variant in the intron 1 splicing donor site of MCP. To assess the pathogenicity of this intronic variant, we conducted functional splicing assay using a minigene construct and quantitative PCR analysis of the MCP transcript, revealing the pathogenicity of the intronic variant. In conclusion, the minigene assay revealed the pathogenicity of the intron 1 splicing donor site variant for the first time. This case showed a severe phenotype of infantile-onset aHUS associated with digenic variants in two complement-related genes.


Assuntos
Complemento C3/genética , Síndrome Hemolítico-Urêmica/genética , Proteína Cofatora de Membrana/genética , Mutação , Processamento de RNA , Idade de Início , Humanos , Lactente , Íntrons , Masculino , Fenótipo , Reação em Cadeia da Polimerase , RNA Mensageiro/genética
4.
Clin Exp Nephrol ; 22(4): 924-930, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29352455

RESUMO

BACKGROUND: Thrombotic microangiopathy (TMA) includes hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). This study examined the epidemiological characteristics of pediatric patients with TMA classified according to etiology. METHODS: The survey evaluated 258 Japanese pediatric patients diagnosed with TMA between 2012 and 2015. RESULTS: The primary diseases responsible for TMA were categorized as TTP (15 cases), Shiga toxin-producing Escherichia coli-associated HUS (STEC-HUS) (166 cases), atypical HUS (aHUS) (40 cases), and secondary TMA (27 cases). The remaining 10 cases were unable to be classified to one of the four categories of the primary disease. Renal replacement therapy was required in the acute phase in 103 patients with TMA, including 65 with STEC-HUS, 22 with aHUS, two with TTP, 10 with secondary TMA, and four unclassified cases. The last observational findings were normal renal function in 95 patients and chronic kidney disease (CKD) stage 1 in 62. For 31 patients, chronic renal insufficiency (CKD stage 2-5) persisted, including four patients with end-stage kidney disease (CKD stage 5). Seventeen patients suffered recurrence of TMA, and eight patients died. CONCLUSION: This study clarified differences in the relative proportions of primary diseases between patients from Japan and North America and Europe. The difference may be attributable to the lower estimated incidence of STEC-HUS in Japan.


Assuntos
Microangiopatias Trombóticas/diagnóstico , Criança , Pré-Escolar , Estudos Transversais , Europa (Continente) , Feminino , Humanos , Japão , Masculino , América do Norte , Microangiopatias Trombóticas/complicações , Microangiopatias Trombóticas/patologia
5.
Biosci Biotechnol Biochem ; 81(12): 2396-2399, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29017394

RESUMO

Gut microbiota of food allergic children was analyzed by high throughput 16S rRNA gene sequencing. Signs of gut dysbiosis, which is likely associated with gut inflammation, was observed in children with food allergies. For example, decreased abundance of genus Akkermansia but increased abundance of Veillonella was found in children with food allergy in comparison with healthy control children.


Assuntos
Disbiose/imunologia , Hipersensibilidade Alimentar/microbiologia , Microbioma Gastrointestinal/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino
6.
Biosci Biotechnol Biochem ; 80(12): 2450-2458, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27581276

RESUMO

Fecal and blood samples of infants with autism spectrum disorders (ASD) and healthy infants were analyzed to investigate the association of altered gut microbiota and ASD development. 16S rRNA gene-based sequencing found that, unlike those of healthy infants, feces of ASD infants had significantly higher and lower abundance of genera Faecalibacterium and Blautia, respectively. Moreover, DNA microarray analysis of peripheral blood mononuclear cells (PBMC) detected more highly than low expressed genes in ASD infants than in healthy infants. Gene Ontology analysis revealed that differentially expressed genes between ASD and healthy infants were involved in interferon (IFN)-γ and type-I IFN signaling pathways. Finally, strong positive correlations between expression of IFN signaling-associated genes in PBMC and fecal abundance of Faecalibacterium were found. Our results strongly suggested that altered gut microbiota in infants resulted from ASD development and was associated with systemic immunity dysregulation, especially chronic inflammation.


Assuntos
Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/microbiologia , Microbioma Gastrointestinal , Leucócitos Mononucleares/metabolismo , Transcriptoma , Transtorno do Espectro Autista/sangue , Transtorno do Espectro Autista/imunologia , Estudos de Casos e Controles , Pré-Escolar , Fezes/microbiologia , Humanos , Lactente
7.
Clin Exp Nephrol ; 20(4): 536-543, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27422619

RESUMO

Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. In 2013, we developed diagnostic criteria to enable early diagnosis and timely initiation of appropriate treatment for aHUS. Recent clinical and molecular findings have resulted in several proposed classifications and definitions of thrombotic microangiopathy and aHUS. Based on recent advances in this field and the emerging international consensus to exclude secondary TMAs from the definition of aHUS, we have redefined aHUS and proposed diagnostic algorithms, differential diagnosis, and therapeutic strategies for aHUS.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/etiologia , Síndrome Hemolítico-Urêmica Atípica/terapia , Humanos , Japão
8.
Pediatr Int ; 58(7): 549-55, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27460397

RESUMO

Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. In 2013, we developed diagnostic criteria to enable early diagnosis and timely initiation of appropriate treatment for aHUS. Recent clinical and molecular findings have resulted in several proposed classifications and definitions of thrombotic microangiopathy and aHUS. Based on recent advances in this field and the emerging international consensus to exclude secondary TMAs from the definition of aHUS, we have redefined aHUS and proposed diagnostic algorithms, differential diagnosis, and therapeutic strategies for aHUS.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Diagnóstico Precoce , Guias de Prática Clínica como Assunto , Síndrome Hemolítico-Urêmica Atípica/epidemiologia , Humanos , Incidência , Japão/epidemiologia
10.
Pediatr Int ; 57(5): 1001-3, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26508183

RESUMO

Non-O157 Shiga toxin-producing Escherichia coli (STEC) strains are increasingly recognized as foodborne pathogens that trigger hemolytic uremic syndrome (HUS). The detection and isolation of these strains is important, but distinguishing their bacteriological profiles is difficult. A 2-year-old girl developed HUS with mild renal involvement 22 days after consuming barbecued meat. Clinical and laboratory findings gradually improved without specific treatment. Because neither enterohemorrhagic E. coli (EHEC) nor Shiga toxins were detected in stool cultures in a clinical laboratory and the patient tested negative for circulating antibodies to O157 lipopolysaccharide, the case was initially diagnosed as probable atypical HUS. Subsequent serodiagnostic microagglutination assay and polymerase chain reaction-based molecular testing, however, indicated the presence of the EHEC O121:H19 strain with stx2. Thus, to correctly diagnose and treat HUS, a system for detecting non-O157 STEC in a clinical setting is urgently needed.


Assuntos
Anticorpos Antibacterianos/análise , DNA Bacteriano/análise , Infecções por Escherichia coli/diagnóstico , Síndrome Hemolítico-Urêmica/etiologia , Escherichia coli Shiga Toxigênica/genética , Pré-Escolar , Diagnóstico Diferencial , Infecções por Escherichia coli/complicações , Infecções por Escherichia coli/microbiologia , Fezes/microbiologia , Feminino , Síndrome Hemolítico-Urêmica/diagnóstico , Humanos , Reação em Cadeia da Polimerase , Sorotipagem , Escherichia coli Shiga Toxigênica/imunologia
12.
Pediatr Int ; 56(1): 1-5, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24548192

RESUMO

Atypical hemolytic uremic syndrome (aHUS) is rare and comprises the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Recently, abnormalities in the mechanisms underlying complement regulation have been focused upon as causes of aHUS. The prognosis for patients who present with aHUS is very poor, with the first aHUS attack being associated with a mortality rate of approximately 25%, and with approximately 50% of cases resulting in end-stage renal disease requiring dialysis. If treatment is delayed, there is a high risk of this syndrome progressing to renal failure. Therefore, we have developed diagnostic criteria for aHUS to enable its early diagnosis and to facilitate the timely initiation of appropriate treatment. We hope these diagnostic criteria will be disseminated to as many clinicians as possible and that they will be used widely.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Técnicas de Diagnóstico Urológico/normas , Guias como Assunto , Nefrologia , Sociedades Médicas , Criança , Humanos , Japão
13.
Clin Exp Nephrol ; 18(1): 4-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24343712

RESUMO

Atypical hemolytic uremic syndrome (aHUS) is rare and comprises the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Recently, abnormalities in the mechanisms underlying complement regulation have been focused upon as causes of aHUS. The prognosis for patients who present with aHUS is very poor, with the first aHUS attack being associated with a mortality rate of ~25 %, and with ~50 % of cases resulting in end-stage renal disease requiring dialysis. If treatment is delayed, there is a high risk of this syndrome progressing to renal failure. Therefore, we have developed diagnostic criteria for aHUS to enable its early diagnosis and to facilitate the timely initiation of appropriate treatment. We hope these diagnostic criteria will be disseminated to as many clinicians as possible and that they will be used widely.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Nefrologia/normas , Pediatria/normas , Síndrome Hemolítico-Urêmica Atípica/sangue , Síndrome Hemolítico-Urêmica Atípica/etiologia , Síndrome Hemolítico-Urêmica Atípica/imunologia , Síndrome Hemolítico-Urêmica Atípica/terapia , Biomarcadores/sangue , Ativação do Complemento , Proteínas do Sistema Complemento , Consenso , Diagnóstico Precoce , Humanos , Contagem de Plaquetas/normas , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco
15.
Mol Immunol ; 54(2): 238-46, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23314101

RESUMO

Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. Approximately 10% of cases are classified as atypical due to the absence of Shiga toxin-producing bacteria as a trigger. Uncontrolled activation of the complement system plays a role in the pathogenesis of atypical HUS (aHUS). Although many genetic studies on aHUS have been published in recent years, only limited data has been gathered in Asian countries. We analyzed the genetic variants of 6 candidate genes and the gene deletion in complement factor H (CFH) and CFH-related genes, examined the prevalence of CFH autoantibodies and evaluated the genotype-phenotype relationship in 10 Japanese patients with aHUS. We identified 7 causative or potentially causative mutations in CFH (p.R1215Q), C3 (p.R425C, p.S562L, and p.I1157T), membrane cofactor protein (p.Y189D and p.A359V) and thrombomodulin (p.T500M) in 8 out of 10 patients. All 7 of the mutations were heterozygous and four of them were novel. Two patients carried CFH p.R1215Q and 3 other patients carried C3 p.I1157T. One patient had 2 causative mutations in different genes. One patient was a compound heterozygote of the 2 MCP mutations. The patients carrying mutations in CFH or C3 had a high frequency of relapse and a worse prognosis. One patient had CFH autoantibodies. The present study identified the cause of aHUS in 9 out of 10 Japanese patients. Since the phenotype-genotype correlation of aHUS has clinical significance in predicting renal recovery and transplant outcome, a comprehensively accurate assessment of molecular variation would be necessary for the proper management of aHUS patients in Japan.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Predisposição Genética para Doença , Síndrome Hemolítico-Urêmica/genética , Adolescente , Síndrome Hemolítico-Urêmica Atípica , Criança , Pré-Escolar , Feminino , Humanos , Japão , Masculino , Mutação , Linhagem , Polimorfismo de Fragmento de Restrição , Adulto Jovem
16.
Vaccine ; 27(52): 7402-8, 2009 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-19747993

RESUMO

Outbreaks of highly pathogenic avian influenza viruses (HPAIVs) would cause disasters worldwide. Various strategies against HPAIVs are required to control damage. It is thought that the use of non-pathogenic avian influenza viruses as live vaccines will be effective in an emergency, even though there might be some adverse effects, because small amounts of live vaccines will confer immunity to protect against HPAIV infection. Therefore, live vaccines have the advantage of being able to be distributed worldwide soon after an outbreak. In the present study, we found that intranasal administration of a live H5N1 subtype non-pathogenic virus induced antibody and cytotoxic T lymphocyte responses and protected mice against H5N1 HPAIV infection. In addition, it was found that a small amount (100 PFU) of the live vaccine was as effective as 100 microg (approximately 10(10-11) PFU of virus particles) of the inactivated whole particle vaccine in mice. Consequently, the use of live virus vaccines might be one strategy for preventing pandemics of HPAIVs in an emergency.


Assuntos
Virus da Influenza A Subtipo H5N1/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Administração Intranasal , Animais , Anticorpos Antivirais/sangue , Células Cultivadas , Injeções Subcutâneas , Camundongos , Camundongos Endogâmicos C57BL , Testes de Neutralização , Infecções por Orthomyxoviridae/imunologia , Linfócitos T Citotóxicos/imunologia , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia
17.
Kokubyo Gakkai Zasshi ; 75(3): 162-7, 2008 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-19044017

RESUMO

Lymphoepithelial cysts occur mainly in the lateral cervical region, but rarely in the parotid gland. We report three cases of lymphoepithelial cysts arising in the parotid gland. These patients presented with a mass in the pre-auricular or infra-auricular region. All masses were mobile and non-tender. The lesions were removed by superficial partial parotidectomy. A definite diagnosis could not be made at initial evaluation, including clinical findings, ultrasound sonography, computed tomography, magnetic resonance imaging, nor radioisotope scintigraphy. Final diagnoses were made by histopathologic evaluation of the excised specimen. In these three cases, histopathologic examination of the mass showed a cystic lesion to be lined by stratified squamous or cuboidal epithelium that was surrounded by a lymphoid tissue with lymphoid follicles, leading to a histopathological diagnosis of lymphoepithelial cyst. The postoperative course was uneventful, and there has been no evidence of recurrence in any of the three cases reported. A review of 52 cases of lymphoepithelial cyst arising in the parotid gland reported in Japanese literature was also made together with the three cases of lymphoepithelial cyst arising in the parotid gland reported here. The results of this review were considered clinical presentation and histopathogenesis of the three cases of lymphoepithelial cyst arising in the parotid gland reported here.


Assuntos
Linfocele/patologia , Linfocele/cirurgia , Doenças Parotídeas/patologia , Doenças Parotídeas/cirurgia , Idoso , Diagnóstico por Imagem , Feminino , Humanos , Linfocele/diagnóstico , Masculino , Pessoa de Meia-Idade , Doenças Parotídeas/diagnóstico , Resultado do Tratamento
18.
Nephrol Dial Transplant ; 23(7): 2254-9, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18223261

RESUMO

BACKGROUND: A pathogenic role of intraglomerular plasmin bound to nephritogenic antigen (nephritis-associated plasmin receptor, NAPlr) and resistant to physiologic inhibitors such as alpha(2)-antiplasmin (alpha(2)-AP) has recently been proposed in acute poststreptococcal glomerulonephritis (APSGN). To confirm this concept, we analysed the urinary profile of plasmin cascade in APSGN patients. METHODS: Urine samples from 10 patients with APSGN, 12 patients with IgA nephropathy (IgAN), 10 patients with streptococcal infection without nephritis (SI) and 10 healthy control subjects were analysed. The alpha(2)-AP-resistant plasmin activity was assessed by a chromogenic assay after alpha(2)-AP was added to each urine sample. Urinary plasminogen activator (PA) and plasmin were further analysed by polyacrylamide gel zymography. Urinary NAPlr was assessed by western blot analysis in selected samples. RESULTS: Urinary alpha(2)-AP-resistant plasmin activity corrected for creatinine concentration (units/g x creatinine) was significantly higher in patients with APSGN (2.99 +/- 0.63) than in patients with IgAN (1.02 +/- 0.20, P < 0.01), SI (0.79 +/- 0.17, P < 0.01), or in healthy control subjects (0.73 +/- 0.18, P < 0.01). This tendency was confirmed by casein gel zymography. However urinary PA activity assessed by plasminogen-casein gel zymography did not differ between groups. NAPlr was detected in the urine of APSGN patients. CONCLUSIONS: We found elevated urinary plasmin activity resistant to alpha(2)-AP, which may be due to urinary excretion of NAPlr in patients with APSGN. This result supports the pathogenic role of the NAPlr-plasmin complex in the development of APSGN. Furthermore, alpha(2)-AP-resistant urinary plasmin activity may be useful as a diagnostic marker for APSGN.


Assuntos
Fibrinolisina/efeitos dos fármacos , Fibrinolisina/urina , Glomerulonefrite/microbiologia , Glomerulonefrite/urina , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/urina , alfa 2-Antiplasmina/farmacologia , Doença Aguda , Adolescente , Adulto , Biomarcadores/urina , Estudos de Casos e Controles , Criança , Pré-Escolar , Creatinina/urina , Glomerulonefrite/diagnóstico , Glomerulonefrite por IGA/urina , Humanos , Pessoa de Meia-Idade , Receptores de Peptídeos/metabolismo , Infecções Estreptocócicas/diagnóstico
19.
Immunology ; 124(2): 155-65, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18205793

RESUMO

We investigated whether a vaccine derived from an apathogenic reassortant type A H5N1 influenza strain could induce immune responses in vivo that mediated protection from highly pathogenic avian influenza virus infection in mice. After two subcutaneous immunizations with formalin-inactivated H5N1 whole virus particles (whole particle vaccine), significant killing specific for cells presenting a nucleoprotein peptide from the vaccine strain of the virus was observed. Similar vaccination with viruses treated with ether and formalin, which are commonly used for humans as ether-split vaccines, induced little or no cytotoxic T-cell response. Furthermore, whole particle vaccines of the apathogenic H5N1 strain were more effective than ether-split vaccines at inducing antibody production able to neutralize a highly pathogenic H5N1 strain. Finally, whole particle vaccines of H5N1 protected mice against infection by an H5N1 highly pathogenic avian influenza virus more effectively than did ether-split vaccines. These results suggest that formalin-inactivated virus particles of apathogenic strains are effective for induction of both cytotoxic T-lymphocyte and antibody responses against highly pathogenic avian influenza viruses in vivo, resulting in protection from infection by a highly pathogenic H5N1 virus.


Assuntos
Anticorpos Antivirais/biossíntese , Virus da Influenza A Subtipo H5N1/imunologia , Vacinas contra Influenza/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Linfócitos T Citotóxicos/imunologia , Adjuvantes Imunológicos , Animais , Especificidade de Anticorpos , Citotoxicidade Imunológica/imunologia , Formaldeído , Adjuvante de Freund , Imunoglobulina G/biossíntese , Virus da Influenza A Subtipo H5N1/fisiologia , Interferon-alfa/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Infecções por Orthomyxoviridae/imunologia , Vacinas de Produtos Inativados/imunologia , Replicação Viral/imunologia
20.
Immunology ; 120(1): 28-37, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17034426

RESUMO

It has recently been shown that immature dendritic cells (DCs) stimulated by a danger signal undergo transient maturation followed by exhaustion. However, the exact mechanism for this has not been elucidated. In this study, we show that interleukin-10 (IL-10) secreted from transiently matured DCs stimulated by danger signals is responsible for this rapid DC exhaustion. Blocking of the autocrine IL-10 enabled transient mature DCs to maintain the mature phenotype for several days. However, these DCs remained phenotypically unstable because the addition of IL-10 altered the transient mature DCs to exhausted DCs. More importantly, stimulation of DCs by CD40 protected transient mature DCs from IL-10-dependent exhaustion, with the result that mature DCs remained stable in the presence of IL-10. Furthermore, in vivo administration of stable mature DCs pulsed with ovalbumin protein induced antigen-specific cytotoxic T lymphocytes (CTLs) effectively, whereas neither exhausted DCs nor transient mature DCs were able to prime a strong antigen-specific CTL response. These results indicate that DC-T cell engagement via CD40-CD154 is required for stable DC maturation leading to effective CTL induction. Otherwise, DCs stimulated solely by a danger signal are temporarily activated, but then rapidly lose their immune-activating capacity under the influence of autocrine IL-10.


Assuntos
Antígenos CD40/imunologia , Células Dendríticas/imunologia , Interleucina-10/imunologia , Animais , Células da Medula Óssea/imunologia , Comunicação Celular/imunologia , Diferenciação Celular/imunologia , Citotoxicidade Imunológica , Feminino , Imunofenotipagem , Interleucina-10/deficiência , Lipopolissacarídeos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Ovalbumina/imunologia , Linfócitos T Citotóxicos/imunologia
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