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1.
Immunol Med ; 43(1): 57-60, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31852362

RESUMO

An eight-year-old girl was admitted for prolonged fever and general fatigue. Bilateral reddened and swollen tonsils covered with white fur and increased numbers of atypical lymphocytes in blood led to a diagnosis of infectious mononucleosis (IM) due to primary Epstein-Barr virus (EBV) infection, which was confirmed by a positive anti-EBV viral capsid antigen IgM antibody reaction. She had a swollen thyroid gland and glycosuria at admission, which persisted after IM resolved. Undetectable thyroid-stimulating hormone (TSH), increased thyroid hormone and elevated HbA1c levels led to a diagnosis of autoimmune polyglandular syndrome type3A, based on the presence of antibodies for TSH receptor and glutamic acid decarboxylase. The clinical significance of EBV infection in the development of autoimmune endocrine disorders has been discussed.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/imunologia , Poliendocrinopatias Autoimunes/etiologia , Poliendocrinopatias Autoimunes/imunologia , Biomarcadores , Criança , Feminino , Hemoglobinas Glicadas , Humanos , Imunoglobulina M , Contagem de Linfócitos , Poliendocrinopatias Autoimunes/diagnóstico , Tireotropina/sangue
3.
Int J Hematol ; 91(5): 808-19, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20428981

RESUMO

B cell-activating factor belonging to the tumor necrosis factor superfamily (BAFF) is a crucial factor for B cell development and is involved in the survival of malignant B cells, but its effect on B cell precursors (BCPs) remains unclear. We investigated BCP acute lymphoblastic leukemia (-ALL) cells for BAFF receptor (-R) expression and compared the effect of BAFF on BCP-ALL cells and Burkitt lymphoma (BL) cells. Expression of BAFF-R was detected in some cell lines and some clinical specimens of both BL and BCP-ALL. BAFF acted on both BL and BCP-ALL cells and promoted proliferation by both. BAFF also inhibited apoptosis by BL cells induced by cross-linking of cell surface molecules and anticancer drugs, but failed to inhibit apoptosis by BCP-ALL cells. BAFF induced prompt and obvious activation of the NF-kappaB signaling pathway in BL cells, but only weak and delayed activation of the pathway in BCP-ALL cells. The results of this study indicate that some BCP-ALL cells and some BL cells express BAFF-R, but that the effects of BAFF on BCP-ALL cells are different from its effects on mature B cell malignancies.


Assuntos
Fator Ativador de Células B/imunologia , Receptor do Fator Ativador de Células B/genética , Linfoma de Burkitt/imunologia , Regulação Leucêmica da Expressão Gênica , Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia , Células Precursoras de Linfócitos B/patologia , Apoptose , Fator Ativador de Células B/genética , Receptor do Fator Ativador de Células B/imunologia , Linfoma de Burkitt/genética , Linfoma de Burkitt/patologia , Antígenos CD40/imunologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Células Precursoras de Linfócitos B/citologia , Células Precursoras de Linfócitos B/imunologia
4.
Hum Gene Ther ; 20(7): 777-83, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19284246

RESUMO

The CH-296 recombinant fragment of human fibronectin is essential for murine leukemia virus (MLV)-derived retroviral transduction of CD34(+) cells for the purpose of stem cell gene therapy. Although the major effect of CH-296 is colocalization of the MLV-derived retrovirus and target cells at specific adhesion domains of CH-296 mediated by integrins expressed on CD34(+) cells, the precise roles of the integrins are unclear. We examined the kinetics of integrin expression on CD34(+) cells during the course of MLV-derived retrovirus-mediated gene transduction with CH-296. Flow cytometry revealed that the levels of both very late activation protein (VLA)-4 and VLA-5 on CD34(+) cells freshly isolated from cord blood were insufficient for effective MLV-derived retroviral transduction. However, increases were achieved during culture for preinduction and MLV-derived retrovirus-mediated gene transduction in the presence of a cocktail of cytokines. In addition, we confirmed by using specific antibodies that inhibition of the cell adhesion mediated by the integrins significantly reduced transduction efficiency, indicating that integrin expression is indeed important for CH-296-based MLV-derived retroviral transduction. Only a few cytokines are capable of inducing integrin expression, and stem cell factor plus thrombopoietin was found to be the minimal combination that was sufficient for effective transduction of an MLV-derived retrovirus based on CH-296. Our findings should be useful for improving the culture conditions for CH-296-based MLV-derived retroviral transduction in stem cell gene therapy.


Assuntos
Antígenos CD34/metabolismo , Fibronectinas/metabolismo , Terapia Genética , Integrinas/metabolismo , Vírus da Leucemia Murina/genética , Células-Tronco/metabolismo , Transdução Genética , Animais , Adesão Celular , Ensaio de Unidades Formadoras de Colônias , Citocinas/metabolismo , Humanos , Cinética , Camundongos , Proteínas Recombinantes/metabolismo , Células-Tronco/citologia
5.
Leuk Res ; 33(7): 908-12, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19243819

RESUMO

The expression of granulysin, a cytolytic protein produced by activated T and NK cells, has been revealed to be correlated with the prognosis of some adult cancer patients. By examination on various childhood lymphoma tissues, we found that granulysin level was especially high in systemic anaplastic large cell lymphoma (ALCL) cases, whereas no close correlation with the expression of CD96, a marker for activated T and NK cells, was observed. We further demonstrated that both ALCL cells in biopsy specimens and cell lines established from ALCL express granulysin, indicating some correlation of granulysin with biological features of ALCL.


Assuntos
Antígenos de Diferenciação de Linfócitos T/genética , Linfoma de Burkitt/genética , Doença de Hodgkin/genética , Linfoma de Células B/genética , Linfoma Difuso de Grandes Células B/genética , Linfoma Anaplásico de Células Grandes/genética , RNA Mensageiro/genética , Adolescente , Adulto , Idoso , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linfoma de Burkitt/metabolismo , Linfoma de Burkitt/patologia , Feminino , Citometria de Fluxo , Doença de Hodgkin/metabolismo , Doença de Hodgkin/patologia , Humanos , Células Matadoras Naturais/metabolismo , Células Matadoras Naturais/patologia , Linfoma de Células B/metabolismo , Linfoma de Células B/patologia , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Linfoma Anaplásico de Células Grandes/metabolismo , Linfoma Anaplásico de Células Grandes/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Adulto Jovem
6.
Immunology ; 128(3): 405-19, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20067540

RESUMO

With an increase in the importance of umbilical cord blood (CB) as an alternative source of haematopoietic progenitors for allogenic transplantation, donor lymphocyte infusion (DLI) with donor CB-derived activated CD4(+) T cells in the unrelated CB transplantation setting is expected to be of increased usefulness as a direct approach for improving post-transplant immune function. To clarify the characteristics of activated CD4(+) T cells derived from CB, we investigated their mRNA expression profiles and compared them with those of peripheral blood (PB)-derived activated CD4(+) T cells. Based on the results of a DNA microarray analysis and quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR), a relatively high level of forkhead box protein 3 (Foxp3) gene expression and a relatively low level of interleukin (IL)-17 gene expression were revealed to be significant features of the gene expression profile of CB-derived activated CD4(+) T cells. Flow cytometric analysis further revealed protein expression of Foxp3 in a portion of CB-derived activated CD4(+) T cells. The low level of retinoic acid receptor-related orphan receptor gamma isoform t (RORgamma t) gene expression in CB-derived activated CD4(+) T cells was speculated to be responsible for the low level of IL-17 gene expression. Our data indicate a difference in gene expression between CD4(+) T cells from CB and those from PB. The findings of Foxp3 expression, a characteristic of regulatory T cells, and a low level of IL-17 gene expression suggest that CB-derived CD4(+) T cells may be a more appropriate source for DLI.


Assuntos
Linfócitos T CD4-Positivos/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Transfusão de Linfócitos , RNA Mensageiro/análise , Linfócitos T Reguladores/metabolismo , Células Sanguíneas/citologia , Transfusão de Sangue Autóloga , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Proliferação de Células , Células Cultivadas , Sangue Fetal/citologia , Fatores de Transcrição Forkhead/genética , Perfilação da Expressão Gênica , Humanos , Interleucina-17/genética , Interleucina-17/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Receptores do Ácido Retinoico/biossíntese , Receptores do Ácido Retinoico/genética , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Receptor gama de Ácido Retinoico
7.
Immunology ; 125(4): 570-90, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18540961

RESUMO

B-cell-activating factor (BAFF) is a survival and maturation factor for B cells belonging to the tumour necrosis factor superfamily. Among three identified functional receptors, the BAFF receptor (BAFF-R) is thought to be responsible for the effect of BAFF on B cells though details of how remain unclear. We determined that a hairy-cell leukaemia line, MLMA, expressed a relatively high level of BAFF-R and was susceptible to apoptosis mediated by either CD20 or B-cell antigen receptor (BCR). Using MLMA cells as an in vitro model of mature B cells, we found that treatment with BAFF could inhibit apoptosis mediated by both CD20 and BCR. We also observed, using immunoblot analysis and microarray analysis, that BAFF treatment induced activation of nuclear factor-kappaB2 following elevation of the expression level of Bcl-2, which may be involved in the molecular mechanism of BAFF-mediated inhibition of apoptosis. Interestingly, BAFF treatment was also found to induce the expression of a series of genes, such as that for CD40, related to cell survival, suggesting the involvement of a multiple mechanism in the BAFF-mediated anti-apoptotic effect. MLMA cells should provide a model for investigating the molecular basis of the effect of BAFF on B cells in vitro and will help to elucidate how B cells survive in the immune system in which BAFF-mediated signalling is involved.


Assuntos
Antígenos CD20/imunologia , Fator Ativador de Células B/farmacologia , Receptores de Antígenos de Linfócitos B/imunologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Linfócitos B/citologia , Antígenos CD40/análise , Antígenos CD40/genética , Linhagem Celular Transformada , Proliferação de Células/efeitos dos fármacos , Depressão Química , Perfilação da Expressão Gênica , Humanos , Immunoblotting , Imunofenotipagem , Leucemia de Células Pilosas , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Recombinantes/farmacologia , Regulação para Cima
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