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2.
Clin Immunol ; 141(3): 357-64, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21996454

RESUMO

Peripheral blood mononuclear cells with T(FH) phenotype from two asymptomatic XLP patients were studied. Normal/high numbers of CXCR5+, CD4+ T cells coexpressing PD-1 were demonstrated. Peripheral blood mononuclear cells (PBMC) from these patients responded to sub-optimal PHA/IL-2 stimulation upregulating ICOS and CD40L and increasing intracellular expression of IL-10, IL-21 and IL-4 by CD4+ T(FH) cells. However when compared to N, the time profile of activation and cytokine synthesis was different in XLP and N. While ICOS and CD40L expression in N decreased after 6-8 days, it continued to increase or was maintained in XLP cultures. Intracellular IL-10, IL-21 and IL-4 reached higher values in XLP than N after 8 days. Rather than the absence of T(FH) cells or their intrinsic inability to respond to stimuli, differences in the time profile of their response could contribute to impair their role as helpers of B lymphocytes.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Transtornos Linfoproliferativos/imunologia , Adulto , Linfócitos T CD4-Positivos/efeitos dos fármacos , Ligante de CD40/biossíntese , Ligante de CD40/imunologia , Células Cultivadas , Éxons , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Proteína Coestimuladora de Linfócitos T Induzíveis/biossíntese , Proteína Coestimuladora de Linfócitos T Induzíveis/imunologia , Interleucina-2/imunologia , Interleucina-2/farmacologia , Interleucinas/imunologia , Interleucinas/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Leucócitos Mononucleares/imunologia , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/genética , Pessoa de Meia-Idade , Mutação , Fito-Hemaglutininas/imunologia , Fito-Hemaglutininas/farmacologia , Proteína Associada à Molécula de Sinalização da Ativação Linfocitária , Linfócitos T Auxiliares-Indutores/imunologia , Regulação para Cima/imunologia
3.
Medicina (B Aires) ; 66(5): 405-14, 2006.
Artigo em Espanhol | MEDLINE | ID: mdl-17137169

RESUMO

Auto or alloantibodies reactive with neutrophils define immune neutropenia. Alloimmune neonatal neutropenia is caused by maternal sensitization to paternal neutrophil antigens, resulting in IgG antibodies that are transferred to the fetus through the placenta. We present the studies in 4 children from 3 families with neutropenia of unknown origin (two of them were brothers). They were evaluated by flow cytometry in parallel with leukoagglutination. Reference values were established for serum reactive IgG in healthy volunteers for three dilutions (1/2, 1/5 and 1/20), both for the autologous reaction (serum and cells of the same individual) and for the heterologous reaction (serum and cells of different individuals). Results were expressed by an index defined by the quotient of the mean fluorescence intensity of the patient's serum divided by that of the reference serum. Serum reactive/agglutinant factors and circulating immune complexes were evaluated in patients and parents serum. Neutrophil specific phenotypes were determined for HNA-1a, HNA-1b and HNA-2a. Reactive IgG/agglutinant factors were found in 4 children. Two maternal sera were reactive against paternal and/or children neutrophils. Circulating immune complexes were detected in 2/4 children sera and were negative in 3/3 maternal sera. Maternal/children incompatibility was detected in the four cases. The three mothers had the same phenotype: homozygous NA1/NA1, NB1+.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/imunologia , Imunoglobulina G/sangue , Neutropenia/imunologia , Neutrófilos/imunologia , Aglutinação/imunologia , Anticorpos Anticitoplasma de Neutrófilos/sangue , Eosinófilos/metabolismo , Feminino , Citometria de Fluxo/métodos , Fator Estimulador de Colônias de Granulócitos , Humanos , Lactente , Contagem de Leucócitos , Masculino , Neutropenia/sangue , Neutrófilos/metabolismo , Fenótipo , Gravidez , Proteínas Recombinantes , Valores de Referência
4.
Clin Exp Immunol ; 147(3): 456-64, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17302894

RESUMO

UNLABELLED: We have analysed the phenotype of T lymphocytes in two X-linked lymphoproliferative disease (XLP) patients with the same SH2D1A mutation differing in initial exposure to Epstein-Barr virus (EBV) and treatment. While memory T lymphocytes (with low CCR7 and CD62L expression) prevailed in both XLP patients, in patient 9, who developed acute infectious mononucleosis (AIM) and received B cell ablative treatment, the predominant phenotype was that of late effector CD8 T cells (CD27-, CD28-, CCR7-, CD62L-, CD45 RA+, perforin+), while in patient 4 (who did not suffer AIM) the prevalent phenotype of CD8 T lymphocytes was similar to that of normal controls (N) or to that of adult individuals who recovered from AIM: CD27+ , CD28+, CCR7-, CD62L-, CD45 RO+ and perforin-. CD57 expression (related to senescence) was also higher in CD8 T cells from patient 9 than in patient 4, AIM or N. Persistently high EBV viral load was observed in patient 9. The results obtained from this limited number of XLP patients suggest that events related to the initial EBV encounter (antigen load, treatment, cytokine environment) may have more weight than lack of SH2D1A in determining the long-term differentiation pattern of CD8 memory T cells.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Transtornos Linfoproliferativos/imunologia , Adulto , Ligante CD27/sangue , Antígenos CD28/sangue , Linfócitos T CD4-Positivos/imunologia , Pré-Escolar , Doenças Genéticas Ligadas ao Cromossomo X/virologia , Herpesvirus Humano 4/isolamento & purificação , Humanos , Memória Imunológica , Imunofenotipagem , Mononucleose Infecciosa/complicações , Mononucleose Infecciosa/imunologia , Interferon gama/biossíntese , Transtornos Linfoproliferativos/virologia , Masculino , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/sangue , Carga Viral
5.
Medicina (B.Aires) ; Medicina (B.Aires);66(5): 405-414, 2006. tab, graf, ilus
Artigo em Espanhol | LILACS | ID: lil-451707

RESUMO

La neutropenia inmune se diagnostica por la presencia de auto o aloanticuerpos reactivos con losneutrófilos. La neutropenia aloinmune neonatal es consecuencia de la sensibilización materna alos antígenos específicos de los neutrófilos paternos que afectan al neonato al atravesar la barrera placentaria. Se presentan 4 casos de niños, 2 de ellos hermanos consanguíneos con doble vínculo. Se estudiaron los sueros de los pacientes y sus padres. Por citometría de flujo se establecen los valores de referencia de la IgG sérica reactiva con los neutrófilos en voluntarios sanos, para 3 diluciones (1/2, 1/5 y 1/20) en reacción autóloga(suero y células de un mismo individuo) y heteróloga (suero y células de diferentes individuos). Los resultadosse expresan por un índice definido como el cociente entre la mediana de la intensidad de fluorescencia media del suero incógnita y la de un suero utilizado como referencia. Por leucoaglutinación se evaluó la dilucióndel suero 1/20. Se determinó el nivel de complejos inmunes circulantes. Se determinó el fenotipo, para los epitopes HNA-1a, HNA-1b y HNA-2a. En los 4 niños se encontró IgG reactiva y/o factores aglutinantes; 2/3 sueros maternos fueron reactivos con los neutrófilos del cónyuge y de los hijos. Los complejos inmunes circulantes fueron positivos en 2/4 sueros negativos en 3/3 sueros maternos. Se encontró incompatibilidad materno-infantil en los 4 casos. Las 3 madres tenían igual fenotipo: homocigotos NA1/NA1, NB1+. En síntesis, se presenta el hallazgo de 4 casos con neutropenia inmune: 3/4 auto-inmune, 1/3 se asocia a complejos inmunes circulantes y 1/4 con neutropenia neonatal aloinmune


Auto or alloantibodies reactive with neutrophils define immune neutropenia. Alloimmune neonatal neutropenia is caused by maternal sensitization to paternal neutrophil antigens, resulting in IgG antibodies that are transferred to the fetus through the placenta. We present the studies in 4 children from 3 families with neutropenia of unknown origin (two of them were brothers). Theywere evaluated by flow cytometry in parallel with leukoagglutination. Reference values were established forserum reactive IgG in healthy volunteers for three dilutions (1/2, 1/5 and 1/20), both for the autologous reaction (serum and cells of the same individual) and for the heterologous reaction (serum and cells of differentindividuals). Results were expressed by an index defined by the quotient of the mean fluorescence intensityof the patient’s serum divided by that of the reference serum. Serum reactive/agglutinant factors and circulating immune complexes were evaluated in patients and parents serum. Neutrophil specific phenotypes weredetermined for HNA-1a, HNA-1b and HNA-2a. Reactive IgG/agglutinant factors were found in 4 children. Twomaternal sera were reactive against paternal and/or children neutrophils. Circulating immune complexes weredetected in 2/4 children sera and were negative in 3/3 maternal sera. Maternal/children incompatibility wasdetected in the four cases. The three mothers had the same phenotype: homozygous NA1/NA1, NB1+


Assuntos
Humanos , Masculino , Feminino , Gravidez , Lactente , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Citometria de Fluxo/métodos , Imunoglobulina G/sangue , Neutropenia/imunologia , Neutrófilos/imunologia , Aglutinação/imunologia , Anticorpos Anticitoplasma de Neutrófilos/sangue , Eosinófilos/metabolismo , Contagem de Leucócitos , Neutropenia/sangue , Neutrófilos/metabolismo , Fenótipo , Valores de Referência
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