Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
J Allergy Clin Immunol ; 130(5): 1153-1158.e2, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22698521

RESUMO

BACKGROUND: Early desensitization of FcεRI-bearing mast cells and basophils has been demonstrated in allergen-specific immunotherapy and drug desensitization. However, its mechanisms have not been elucidated in detail. Histamine is one of the main mediators released on FcεRI triggering of basophils and mast cells, and it exerts its functions through histamine receptors (HRs). OBJECTIVES: We sought to investigate HR expression on basophils of patients undergoing venom immunotherapy (VIT) and its effect on allergen, IgE, and FcεRI cross-linking-mediated basophil function and mediator release. METHODS: Basophils were purified from the peripheral blood of patients undergoing VIT and control subjects and were studied functionally by using real-time PCR, flow cytometry and ELISA assays. RESULTS: Rapid upregulation of H2R within the first 6 hours of the build-up phase of VIT was observed. H2R strongly suppressed FcεRI-induced activation and mediator release of basophils, including histamine and sulfidoleukotrienes, as well as cytokine production in vitro. CONCLUSION: Immunosilencing of FcεRI-activated basophils by means of selective suppression mediated by H2R might be highly relevant for the very early induction of allergen tolerance and the so-called desensitization effect of VIT.


Assuntos
Basófilos/efeitos dos fármacos , Hipersensibilidade/terapia , Mordeduras e Picadas de Insetos/terapia , Receptores Histamínicos H2/metabolismo , Receptores de IgE/antagonistas & inibidores , Peçonhas/uso terapêutico , Adolescente , Adulto , Idoso , Animais , Basófilos/imunologia , Venenos de Abelha/uso terapêutico , Células Cultivadas , Feminino , Humanos , Hipersensibilidade/imunologia , Terapia de Imunossupressão , Mordeduras e Picadas de Insetos/imunologia , Masculino , Pessoa de Meia-Idade , Receptores de IgE/metabolismo , Venenos de Vespas/urina , Adulto Jovem
2.
Eukaryot Cell ; 9(10): 1466-75, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20693305

RESUMO

The precise subcellular localization of the components of the cyclic AMP (cAMP) signaling pathways is a crucial aspect of eukaryotic intracellular signaling. In the human pathogen Trypanosoma brucei, the strict control of cAMP levels by cAMP-specific phosphodiesterases is essential for parasite survival, both in cell culture and in the infected host. Among the five cyclic nucleotide phosphodiesterases identified in this organism, two closely related isoenzymes, T. brucei PDEB1 (TbrPDEB1) (PDEB1) and TbrPDEB2 (PDEB2) are predominantly responsible for the maintenance of cAMP levels. Despite their close sequence similarity, they are distinctly localized in the cell. PDEB1 is mostly located in the flagellum, where it forms an integral part of the flagellar skeleton. PDEB2 is mainly located in the cell body, and only a minor part of the protein localizes to the flagellum. The current study, using transfection of procyclic trypanosomes with green fluorescent protein (GFP) reporters, demonstrates that the N termini of the two enzymes are essential for determining their final subcellular localization. The first 70 amino acids of PDEB1 are sufficient to specifically direct a GFP reporter to the flagellum and to lead to its detergent-resistant integration into the flagellar skeleton. In contrast, the analogous region of PDEB2 causes the GFP reporter to reside predominantly in the cell body. Mutagenesis of selected residues in the N-terminal region of PDEB2 demonstrated that single amino acid changes are sufficient to redirect the reporter from a cell body location to stable integration into the flagellar skeleton.


Assuntos
3',5'-AMP Cíclico Fosfodiesterases/química , 3',5'-AMP Cíclico Fosfodiesterases/metabolismo , Citoesqueleto/enzimologia , Flagelos/enzimologia , Transdução de Sinais , Trypanosoma brucei brucei/enzimologia , 3',5'-AMP Cíclico Fosfodiesterases/genética , Sequência de Aminoácidos , Animais , AMP Cíclico/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Isoenzimas/química , Isoenzimas/genética , Isoenzimas/metabolismo , Dados de Sequência Molecular , Proteínas de Protozoários/química , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Trypanosoma brucei brucei/genética , Trypanosoma brucei brucei/metabolismo
3.
J Exp Med ; 205(12): 2887-98, 2008 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-19001136

RESUMO

High dose bee venom exposure in beekeepers by natural bee stings represents a model to understand mechanisms of T cell tolerance to allergens in healthy individuals. Continuous exposure of nonallergic beekeepers to high doses of bee venom antigens induces diminished T cell-related cutaneous late-phase swelling to bee stings in parallel with suppressed allergen-specific T cell proliferation and T helper type 1 (Th1) and Th2 cytokine secretion. After multiple bee stings, venom antigen-specific Th1 and Th2 cells show a switch toward interleukin (IL) 10-secreting type 1 T regulatory (Tr1) cells. T cell regulation continues as long as antigen exposure persists and returns to initial levels within 2 to 3 mo after bee stings. Histamine receptor 2 up-regulated on specific Th2 cells displays a dual effect by directly suppressing allergen-stimulated T cells and increasing IL-10 production. In addition, cytotoxic T lymphocyte-associated antigen 4 and programmed death 1 play roles in allergen-specific T cell suppression. In contrast to its role in mucosal allergen tolerance, transforming growth factor beta does not seem to be an essential player in skin-related allergen tolerance. Thus, rapid switch and expansion of IL-10-producing Tr1 cells and the use of multiple suppressive factors represent essential mechanisms in immune tolerance to a high dose of allergens in nonallergic individuals.


Assuntos
Alérgenos , Venenos de Abelha , Abelhas , Tolerância Imunológica/fisiologia , Interleucina-10/metabolismo , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores , Adulto , Idoso , Alérgenos/administração & dosagem , Alérgenos/imunologia , Animais , Venenos de Abelha/administração & dosagem , Venenos de Abelha/imunologia , Citocinas/sangue , Citocinas/genética , Citocinas/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional , Ocupações , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Receptores Histamínicos/genética , Receptores Histamínicos/imunologia , Estações do Ano , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo
4.
J Allergy Clin Immunol ; 122(5): 1001-1007.e4, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18845330

RESUMO

BACKGROUND: H1 antihistamines increase safety during allergen-specific immunotherapy and might influence the outcome because of immunoregulatory effects. OBJECTIVE: We sought to analyze the influence of 5 mg of levocetirizine (LC) on the safety, efficacy, and immunologic effects of ultrarush honeybee venom immunotherapy (BVIT). METHOD: In a double-blind, placebo-controlled study 54 patients with honeybee venom allergy received LC or placebo from 2 days before BVIT to day 21. Side effects during dose increase and systemic allergic reactions (SARs) to a sting challenge after 120 days were analyzed. Allergen-specific immune response was investigated in skin, serum, and allergen-stimulated T-cell cultures. RESULTS: Side effects were significantly more frequent in patients receiving placebo. Four patients receiving placebo dropped out because of side effects. SARs to the sting challenge occurred in 8 patients (6 in the LC group and 2 in the placebo group). Seven SARs were only cutaneous, and 1 in the placebo group was also respiratory. Difference of SARs caused by the sting challenge was insignificant. Specific IgG levels increased significantly in both groups. Major allergen phospholipase A(2)-stimulated T cells from both groups showed a slightly decreased proliferation. The decrease in IFN-gamma and IL-13 levels with placebo was not prominent with LC, whereas IL-10 levels showed a significant increase in the LC group only. Decreased histamine receptor (HR)1/HR2 ratio in allergen-specific T cells on day 21 in the placebo group was prevented by LC. CONCLUSIONS: LC reduces side effects during dose increase without influencing the efficacy of BVIT. LC modulates the natural course of allergen-specific immune response and affects the expression of HRs and cytokine production by allergen-specific T cells.


Assuntos
Venenos de Abelha , Cetirizina/imunologia , Dessensibilização Imunológica , Antagonistas dos Receptores Histamínicos H1/imunologia , Hipersensibilidade/prevenção & controle , Adolescente , Adulto , Venenos de Abelha/efeitos adversos , Venenos de Abelha/imunologia , Cetirizina/uso terapêutico , Dessensibilização Imunológica/efeitos adversos , Método Duplo-Cego , Feminino , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Humanos , Hipersensibilidade/etiologia , Hipersensibilidade/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
5.
Eur J Immunol ; 36(2): 380-8, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16365913

RESUMO

The family of IL-10-related cytokines includes several human members, IL-19, IL-20, IL-22, IL-24 and IL-26, and a series of herpesviral and poxviral paralogs. Some of these cytokines share common receptor subunits. In this study, we investigated the effects of these cytokines on naive T cell differentiation, antigen-specific T cell suppression, survival ad expression of surface markers in comparison to IL-10 and cytomegalovirus (CMV)-IL-10. Human CD45RA(+) T cells were stimulated in the presence of IL-10-family cytokines in sequential 12-day cycles. After three to four cycles of stimulation, IL-10 and CMV-IL-10 led to increased IFN-gamma and IL-10 but decreased IL-4 and IL-13. Interestingly, long-term exposure of T cells to IL-19, IL-20 and IL-22 down-regulated IFN-gamma but up-regulated IL-4 and IL-13 in T cells and supported the polarization of naive T cells to Th2-like cells. In contrast, neutralization of endogenous IL-22 activity by IL-22-binding protein decreased IL-4, IL-13 and IFN-gamma synthesis. The antigen-specific suppressor activity of IL-10 and CMV-IL-10 was not observed for any of the other IL-10-family cytokines. These data demonstrate that IL-19, IL-20 and IL-22 may participate in T cell-mediated diseases by distinct regulation of T cell cytokine profiles.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Citocinas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Células Th2/imunologia , Proteínas Virais/farmacologia , Diferenciação Celular/imunologia , Células Cultivadas , Citocinas/biossíntese , Citocinas/imunologia , Regulação da Expressão Gênica/imunologia , Humanos , Antígenos Comuns de Leucócito/biossíntese , Antígenos Comuns de Leucócito/imunologia , Células Th2/citologia , Células Th2/metabolismo , Fatores de Tempo , Proteínas Virais/imunologia
6.
Eur J Immunol ; 35(11): 3268-76, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16206231

RESUMO

Novel approaches for the prevention of allergy are required, because of the inevitably increasing prevalence of allergic diseases during the last 30 years. Here, a recombinant chimeric protein, which comprises the whole amino acid sequences of three bee venom major allergens has been engineered and used in prevention of bee venom sensitization in mice. Phospholipase A2 (Api m 1), hyaluronidase (Api m 2) and melittin (Api m 3) fragments with overlapping amino acids were assembled in a different order in the Api m (1/2/3) chimeric protein, which preserved entire T cell epitopes, whereas B cell epitopes of all three allergens were abrogated. Accordingly, IgE cross-linking leading to mast cell and basophil mediator release was profoundly reduced in humans. Supporting these findings, the Api m (1/2/3) induced 100 to 1000 times less type-1 skin test reactivity in allergic patients. Treatment of mice with Api m (1/2/3) led to a significant reduction of specific IgE development towards native allergen, representing a protective vaccine effect in vivo. These results demonstrate a novel prototype of a preventive allergy vaccine, which preserves the entire T cell epitope repertoire, but bypasses induction of IgE against native allergen, and side effects related to mast cell/basophil IgE FcepsilonRI cross-linking in sensitized individuals.


Assuntos
Sítios de Ligação de Anticorpos , Epitopos de Linfócito T/imunologia , Hipersensibilidade/prevenção & controle , Imunoglobulina E/metabolismo , Mordeduras e Picadas de Insetos/imunologia , Linfócitos T/imunologia , Alérgenos/administração & dosagem , Alérgenos/imunologia , Alérgenos/metabolismo , Animais , Antígenos de Plantas , Abelhas , Células Cultivadas , Epitopos de Linfócito T/administração & dosagem , Epitopos de Linfócito T/metabolismo , Feminino , Humanos , Hialuronoglucosaminidase/administração & dosagem , Hialuronoglucosaminidase/imunologia , Hialuronoglucosaminidase/metabolismo , Hipersensibilidade/imunologia , Hipersensibilidade/terapia , Imunoglobulina E/biossíntese , Imunoglobulina G/biossíntese , Mordeduras e Picadas de Insetos/terapia , Proteínas de Insetos , Camundongos , Camundongos Endogâmicos C57BL , Fosfolipases A/administração & dosagem , Fosfolipases A/imunologia , Fosfolipases A/metabolismo , Fosfolipases A2 , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA