Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 9 de 9
Filtrar
1.
Nat Med ; 3(8): 849-54, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9256274

RESUMO

An adjuvant role for certain short bacterial immunostimulatory DNA sequences (ISSs) has recently been proposed on the basis of their ability to stimulate T helper-1 (Th1) responses in gene-vaccinated animals. We report here that noncoding, ISS-enriched plasmid DNAs or ISS oligonucleotides (ISS-ODNs) potently stimulate immune responses to coadministered antigens. The ISS-DNAs suppress IgE synthesis, but promote IgG and interferon-gamma (IFN-gamma) production. They furthermore initiate the production of IFN-gamma, IFN-alpha, IFN-beta, and interleukins 12 and 18, all of which foster Th1 responses and enhance cell-mediated immunity. Consideration should be given to adding noncoding DNA adjuvants to inactivated or subunit viral vaccines that, by themselves, provide only partial protection from infection.


Assuntos
Adjuvantes Imunológicos , DNA/imunologia , Ativação Linfocitária/genética , Células Th1/imunologia , Animais , Formação de Anticorpos/genética , DNA/genética , Feminino , Imunoglobulina E/biossíntese , Imunoglobulina G/biossíntese , Interferons/biossíntese , Interleucinas/biossíntese , Ativação de Macrófagos/genética , Camundongos , Camundongos Endogâmicos BALB C , beta-Galactosidase/imunologia
2.
Toxicology ; 93(2-3): 289-99, 1994 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-7974520

RESUMO

The toxic oil syndrome (TOS), a multisystemic disease, that occurred in Spain in 1981, was caused by the ingestion of rapeseed oil denatured with 2% aniline. Due to the clinical course of the disease, immunopathological mechanisms have been suspected but a direct connection was never demonstrated. To analyse this possibility, we determined several immunological parameters in the sera of patients with TOS and without the disease, using a case-control design: total immunoglobulins, IgG and IgE antibodies against different toxic agents (oleylanilide, aniline, linoleyl-anilide, and 3-phenylaminopropane-1-2-diol), autoantibodies, cytokines (IL-4, IL-6, TNF, GM-CSF) and soluble receptors (sCD23 and sIL-2R). We detected high levels of sIL-2R in TOS patients compared to controls (P < 0.0001). A higher levels of sCD23 and IgE were also found. In addition, the response to oleyl-anilide of peripheral blood lymphocytes from TOS patients was studied and a significant proliferative response in 30% of TOS patients versus 5% controls was observed. Our data support the implication of the immune system in the acute phase of TOS, with a possible activation of T-cells and release of cytokines, that could explain some of the clinical findings in this phase of the disease.


Assuntos
Brassica , Óleos de Plantas/intoxicação , Anilidas/imunologia , Autoanticorpos/sangue , Estudos de Casos e Controles , Ácidos Graxos Monoinsaturados , Fator Estimulador de Colônias de Granulócitos e Macrófagos/análise , Humanos , Imunoglobulinas/sangue , Ativação Linfocitária , Ácidos Oleicos/imunologia , Óleo de Brassica napus , Receptores de IgE/análise , Receptores de Interleucina-2/análise , Síndrome , Linfócitos T/imunologia
4.
Int Immunol ; 11(7): 1111-8, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10383944

RESUMO

Bacterial genomic DNA, plasmid DNA (pDNA) and synthetic oligodeoxynucleotides (ODN) containing immunostimulatory DNA sequences (ISS) have been proposed to foster a Th1 response via the release of type 1 cytokines from macrophages, dendritic cells, NK cells and B cells. In this study, we show that ISS-enriched DNA up-regulates a distinct profile of cell surface molecules on macrophages and B cells in vitro and in vivo. ISS-ODN and ISS-containing pDNA enhanced the expression of antigen presentation molecules (MHC class I and II), co-stimulatory molecules (B7-1, B7-2 and CD40), cytokine receptors (IFN-gamma receptor and IL-2 receptor), an adhesion molecule (ICAM-1) and an Fc receptor (Fcgamma receptor) on murine B cells or bone marrow-derived macrophages. The increased expression of these surface molecules is seen in purified cell populations and is largely independent of the effects of type 1 cytokines. Splenic antigen-presenting cells stimulated with ISS-ODN in vivo efficiently activate naive T cells and bias their differentiation toward a Th1 phenotype in vitro. Thus, the induction of both type 1 cytokines and a distinct profile of cell surface molecules contributes to the potent immunostimulatory effects of ISS-containing DNA on innate and adaptive immunity.


Assuntos
Adjuvantes Imunológicos/farmacologia , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/metabolismo , DNA Bacteriano/imunologia , DNA Viral/imunologia , Proteínas de Membrana/imunologia , Animais , Linfócitos B/imunologia , Linfócitos B/metabolismo , Células da Medula Óssea/imunologia , DNA Bacteriano/genética , DNA Bacteriano/farmacologia , DNA Viral/genética , DNA Viral/farmacologia , Feminino , Ativação Linfocitária/imunologia , Proteínas de Membrana/biossíntese , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Oligonucleotídeos/imunologia , Oligonucleotídeos/farmacologia , Baço/citologia , Linfócitos T/imunologia , Células Th1/imunologia , Regulação para Cima
5.
Biochem Biophys Res Commun ; 172(2): 523-8, 1990 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-2241952

RESUMO

A method to isolate the major allergen from olive pollen (Ole e I) in high yield is described. The allergenic fraction has been separated into 3 subfractions by reverse-phase HPLC. All these fractions were reactive to allergic sera from olive-sensitized patients, giving similar responses. No significant differences were observed between the amino acid compositions of these three proteins. The amino acid sequence of the first 27 amino acid residues from the N-terminal end is given. No homologies have been detected between Ole e I and other known allergens obtained from pollen.


Assuntos
Alérgenos/isolamento & purificação , Pólen/análise , Alérgenos/química , Sequência de Aminoácidos , Cromatografia Líquida de Alta Pressão , Eletroforese em Gel de Poliacrilamida , Humanos , Hipersensibilidade , Dados de Sequência Molecular , Peso Molecular , Fragmentos de Peptídeos/isolamento & purificação , Árvores
6.
Immunology ; 83(1): 155-60, 1994 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-7529744

RESUMO

Murine eosinophils express the low-affinity Fc gamma receptors recognized by the monoclonal antibody (mAb) 2.4G2, which are involved in the activation of these cells. We have studied the membrane and RNA expression of the low-affinity Fc gamma receptors on murine eosinophils stimulated by granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-gamma (IFN-gamma), and interleukin-4 (IL-4). Flow cytometric analysis (FACS) of eosinophils incubated with GM-CSF and IFN-gamma showed an up-regulation on the expression of these receptors with a maximal effect at 24 hr. IL-4 failed to induce any positive or negative effect in these cells. To assess the pattern of expression of the low-affinity Fc gamma receptors on eosinophils, Northern blot analyses were carried out using specific cDNA probes encoding for the Fc gamma RII and Fc gamma RIII. Murine eosinophils constitutively express transcripts for Fc gamma RII and RIII. Incubation with GM-CSF from 3 to 12 hr produced a potent induction of the two transcripts studied (Fc gamma RII and RIII). IFN-gamma did not induce any important up-regulation of the two transcripts from 3 to 12 hr of incubation. By contrast, IL-4 produced a marked inhibition of both transcripts at 24 hr of incubation. Expression of the gamma-chain transcript which is associated with Fc gamma RIII has been detected on freshly isolated eosinophils. This study demonstrates a different regulation pattern of these receptors depending on the cytokine or growth factor used to stimulate murine eosinophils.


Assuntos
Citocinas/imunologia , Eosinófilos/imunologia , Receptores de IgG/análise , Animais , Northern Blotting , Células Cultivadas , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Interferon gama/imunologia , Interleucina-4/imunologia , Camundongos , Camundongos Endogâmicos BALB C , RNA/genética , Receptores de IgG/genética , Proteínas Recombinantes/imunologia , Regulação para Cima/imunologia
7.
J Immunol ; 161(12): 7054-62, 1998 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-9862743

RESUMO

We have used a mouse model of allergen-induced airway hyperresponsiveness to demonstrate that immunostimulatory DNA sequences (ISS) containing a CpG DNA motif significantly inhibit airway eosinophilia and reduce responsiveness to inhaled methacholine. ISS not only inhibited eosinophilia of the airway (by 93%) and lung parenchyma (91%), but also significantly inhibited blood eosinophilia (86%), suggesting that ISS was exerting a significant effect on the bone marrow production of eosinophils. The inhibition of the bone marrow production of eosinophils by 58% was associated with a significant inhibition of T cell-derived cytokine generation (IL-5, granulocyte-macrophage CSF, and IL-3). ISS exerted this inhibitory effect on T cell cytokine production indirectly by stimulating monocytes/macrophages and NK cells to generate IL-12 and IFNs. The onset of the ISS effect on reducing the number of tissue eosinophils was both immediate (within 1 day of administration) and sustained (lasted 6 days), and was not due to ISS directly inducing eosinophil apoptosis. ISS was effective in inhibiting eosinophilic airway inflammation when administered either systemically (i.p.), or mucosally (i.e., intranasally or intratracheally). Interestingly, a single dose of ISS inhibited airway eosinophilia as effectively as daily injections of corticosteroids for 7 days. Moreover, while both ISS and corticosteroids inhibited IL-5 generation, only ISS was able to induce allergen-specific IFN-gamma production and redirect the immune system toward a Th1 response. Thus, systemic or mucosal administration of ISS before allergen exposure could provide a novel form of active immunotherapy in allergic diseases.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Alérgenos/toxicidade , Hiper-Reatividade Brônquica/prevenção & controle , Ilhas de CpG , Interleucina-5/biossíntese , Oligodesoxirribonucleotídeos/uso terapêutico , Eosinofilia Pulmonar/prevenção & controle , Adjuvantes Imunológicos/farmacologia , Administração Intranasal , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Medula Óssea/patologia , Hiper-Reatividade Brônquica/etiologia , Hiper-Reatividade Brônquica/imunologia , Testes de Provocação Brônquica , Dessensibilização Imunológica , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Eosinófilos/patologia , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/biossíntese , Síndrome Hipereosinofílica/etiologia , Síndrome Hipereosinofílica/imunologia , Síndrome Hipereosinofílica/prevenção & controle , Interferon gama/biossíntese , Interleucina-3/biossíntese , Cloreto de Metacolina , Camundongos , Camundongos Endogâmicos BALB C , Oligodesoxirribonucleotídeos/administração & dosagem , Oligodesoxirribonucleotídeos/farmacologia , Ovalbumina/imunologia , Pletismografia Total , Eosinofilia Pulmonar/etiologia , Eosinofilia Pulmonar/imunologia , Células Th2/imunologia , Traqueia/patologia
8.
Int Arch Allergy Immunol ; 104(2): 160-70, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-7515294

RESUMO

Ole e I is the major allergen derived from olive tree pollen (Olea europaea) and it is composed of two polypeptides with molecular weights (MWs) of 18 and 20 kD. A panel of six monoclonal antibodies (mAbs) has been prepared and used to map antigenic determinants on this molecule. Four epitope determinants have been identified on Ole e I. Using the purified mAbs produced against Ole e I, we have analyzed the common epitope determinants in olive (O. europaea) and different Oleaceae pollens: ash (Fraxinus excelsior); privet (Ligustrum vulgare); lilac (Syringa vulgaris), and forsythia (Forsythia suspensa). ELISA showed three reactivity groups depending on the recognition of monoclonal antibodies: (1) olive and ash; (2) olive, ash, privet and lilac; and (3) olive, ash, privet, lilac and forsythia. Immunoblotting studies on Oleaceae pollen extracts with these mAbs showed a very similar cross-reactivity pattern. The 18- and 20-kD MW proteins were present in each pollen, except in the case of forsythia. In this case the reactivity pattern was associated with 50- to 55-kD protein bands. This band was recognized by a pool of sera from olive-allergic patients. Finally, ultrastructural localization of Ole e I antigen was performed on the mature olive pollen grain. Ole e I was located in association with dilated endoplasmic reticulum cisternae. Pollen grain walls, nuclei and cytoplasmic organelles were totally devoid of the allergen.


Assuntos
Alérgenos , Epitopos/análise , Proteínas de Plantas/imunologia , Pólen/imunologia , Animais , Anticorpos Monoclonais/imunologia , Antígenos de Plantas , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina E/imunologia , Peso Molecular , Proteínas de Plantas/análise
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA