Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 14 de 14
Filtrar
1.
Immunity ; 45(2): 319-32, 2016 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-27521268

RESUMO

Interferon regulatory factor-5 (IRF5), a transcription factor critical for the induction of innate immune responses, contributes to the pathogenesis of the autoimmune disease systemic lupus erythematosus (SLE) in humans and mice. Lyn, a Src family kinase, is also implicated in human SLE, and Lyn-deficient mice develop an SLE-like disease. Here, we found that Lyn physically interacted with IRF5 to inhibit ubiquitination and phosphorylation of IRF5 in the TLR-MyD88 pathway, thereby suppressing the transcriptional activity of IRF5 in a manner independent of Lyn's kinase activity. Conversely, Lyn did not inhibit NF-κB signaling, another major branch downstream of MyD88. Monoallelic deletion of Irf5 alleviated the hyperproduction of cytokines in TLR-stimulated Lyn(-/-) dendritic cells and the development of SLE-like symptoms in Lyn(-/-) mice. Our results reveal a role for Lyn as a specific suppressor of the TLR-MyD88-IRF5 pathway and illustrate the importance of fine-tuning IRF5 activity for the maintenance of immune homeostasis.


Assuntos
Autoimunidade , Células Dendríticas/imunologia , Fatores Reguladores de Interferon/metabolismo , Lúpus Eritematoso Sistêmico/imunologia , Quinases da Família src/metabolismo , Animais , Células Cultivadas , Citocinas/metabolismo , Humanos , Tolerância Imunológica , Imunidade Inata , Fatores Reguladores de Interferon/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Fosforilação , Ligação Proteica , Transdução de Sinais , Receptores Toll-Like/metabolismo , Ativação Transcricional , Ubiquitinação , Quinases da Família src/genética
2.
Gene Ther ; 29(10-11): 636-642, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-34987192

RESUMO

Previously, we developed a chimeric adenovirus type 5 with type 35 fiber (Ad5/35), which has high tropism to dendritic cells and low hepatoxicity. For further clinical use, we constructed two recombinant vectors expressing human immunodeficiency virus 1 (HIV-1) clade C gag (Ad5/35-Cgag and MVA-Cgag). The biodistribution of the two viral vectors in a mouse model and immunity in monkeys were assessed. The mice received a single intramuscular injection with the vectors alone. The gag gene in the tissues were periodically detected using a real-time quantitative polymerase chain reaction. The distribution of Ad5/35 was also detected using an in vivo imaging system, followed by luciferase-expressing Ad5/35 administration. We found that Ad5/35-Cgag DNA and luciferase activity were detectable until 8 weeks post-administration, whereas MVA-Cgag was undetectable 72 h post-administration. Furthermore, viral administration did not increase serum aspartate aminotransferase and alanine aminotransferase levels in either mouse or monkey models. Moreover, intramuscular administration of Ad5/35-Cgag induced the gag-specific antibody level and IFNγ-secreting PBMCs, the boost with MVA-Cgag further increased the responses and lasted more than 20 weeks from the initial administration. These data demonstrate that Ad5/35 and MVA vectors are safe for in vivo use, and prime-boost with Ad5/35-MVA vaccines is suitable for clinical use against HIV-1 clade C.


Assuntos
Vacinas contra a AIDS , Infecções por Adenoviridae , HIV-1 , Vacinas de DNA , Vacínia , Humanos , Camundongos , Animais , HIV-1/genética , Adenoviridae/genética , Vacinas contra a AIDS/genética , Distribuição Tecidual , Vaccinia virus/genética , Vetores Genéticos/genética , Vacinas Sintéticas/genética
3.
Sci Rep ; 11(1): 18046, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34508131

RESUMO

Chronic myeloid leukemia (CML) is a form of myeloproliferative neoplasm caused by the oncogenic tyrosine kinase BCR-ABL. Although tyrosine kinase inhibitors have dramatically improved the prognosis of patients with CML, several problems such as resistance and recurrence still exist. Immunological control may contribute to solving these problems, and it is important to understand why CML patients fail to spontaneously develop anti-tumor immunity. Here, we show that differentiation of conventional dendritic cells (cDCs), which are vital for anti-tumor immunity, is restricted from an early stage of hematopoiesis in CML. In addition, we found that monocytes and basophils, which are increased in CML patients, express high levels of PD-L1, an immune checkpoint molecule that inhibits T cell responses. Moreover, RNA-sequencing analysis revealed that basophils express genes related to poor prognosis in CML. Our data suggest that BCR-ABL not only disrupts the "accelerator" (i.e., cDCs) but also applies the "brake" (i.e., monocytes and basophils) of anti-tumor immunity, compromising the defense against CML cells.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/etiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Microambiente Tumoral/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores , Medula Óssea/imunologia , Medula Óssea/metabolismo , Medula Óssea/patologia , Carcinogênese/genética , Carcinogênese/imunologia , Biologia Computacional/métodos , Bases de Dados Genéticas , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Células Dendríticas/patologia , Modelos Animais de Doenças , Suscetibilidade a Doenças , Feminino , Perfilação da Expressão Gênica , Hematopoese/genética , Hematopoese/imunologia , Humanos , Imunidade/genética , Imunofenotipagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Camundongos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neutrófilos/imunologia , Neutrófilos/metabolismo , Transcriptoma , Microambiente Tumoral/genética , Adulto Jovem
4.
Sci Rep ; 10(1): 14195, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32848167

RESUMO

Oncoprotein E6 of high-risk human papillomavirus (HPV) plays a critical role in inducing cell immortalization and malignancy. E6 downregulates caspase-dependent pathway through the degradation of p53. However, the effect of HPV E6 on other pathways is still under investigation. In the present study, we found that HPV E6 directly binds to all three forms (precursor, mature, and apoptotic) of apoptosis-inducing factor (AIF) and co-localizes with apoptotic AIF. This binding induced MG132-sensitive reduction of AIF expression in the presence of E6 derived from HPV16 (16E6), a cancer-causing type of HPV. Conversely, E6 derived from a non-cancer-causing type of HPV, HPV6 (6E6), did not reduce the levels of AIF despite its interaction with AIF. Flow cytometric analysis revealed that 16E6, but not 6E6, suppressed apoptotic AIF-induced chromatin degradation (an indicator of caspase-independent apoptosis) and staurosporine (STS, a protein kinase inhibitor)-induced apoptosis. AIF knockdown reduced STS-induced apoptosis in both of 16E6-expressing and 6E6-expressing cells; however, the reduction in 16E6-expressing cells was lower than that in 6E6-expressing cells. These findings indicate that 16E6, but not 6E6, blocks AIF-mediated apoptosis, and that AIF may represent a novel therapeutic target for HPV-induced cervical cancer.


Assuntos
Fator de Indução de Apoptose/metabolismo , Proteínas Oncogênicas Virais/metabolismo , Proteínas Repressoras/metabolismo , Apoptose , Cromatina/metabolismo , Células HEK293 , Humanos , Complexo de Endopeptidases do Proteassoma/metabolismo
5.
J Invest Dermatol ; 124(6): 1141-8, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15955088

RESUMO

Tight-skin (Tsk/+) mice develop a disease similar to human scleroderma, characterized by the spontaneous appearance of cutaneous hyperplasia, anti-nuclear antibodies, and emphysema. T helper (Th) 2 cells secreting interleukin (IL)-4 are known to play a critical role in the etiopathogenesis of this disease. Th2-mediated responses can be blocked by treatment with synthetic oligodeoxynucleotides (ODN) containing immunomodulatory CpG motifs. Thus, we examined whether CpG ODN might be of therapeutic benefit in Tsk/+ mice. Administering CpG ODN to Tsk/+ mice every 3 wk starting at 1 wk of age abrogated skin fibrosis. This reduction in skin thickness persisted even after the cessation of therapy, and was accompanied by increased serum levels of IL-12 and an increased ratio of T cells available to secrete interferon-gamma rather than IL-4. CpG ODN therapy also reduced autoantibody production, but did not inhibit the incidence of lung emphysema. Delaying the initiation of CpG ODN treatment until 6 wk of age failed to prevent skin disease. These results indicate that by preferentially promoting the development of a Th1-biased immune milieu in young Tsk/+ mice, CpG ODN can ameliorate Th2-driven scleroderma-like syndrome.


Assuntos
Adjuvantes Imunológicos/farmacologia , Oligodesoxirribonucleotídeos/farmacologia , Proteínas Tirosina Quinases/metabolismo , Esclerodermia Localizada/prevenção & controle , Células Th1/imunologia , Animais , Anticorpos Antinucleares/sangue , Formação de Anticorpos , Modelos Animais de Doenças , Fibrose , Interferon gama/biossíntese , Interleucina-12/biossíntese , Interleucina-4/biossíntese , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes/genética , Proteínas Tirosina Quinases/genética , Esclerodermia Localizada/genética , Pele/efeitos dos fármacos , Pele/patologia , Fatores de Tempo
6.
J Invest Dermatol ; 125(6): 1156-62, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16354185

RESUMO

Under conventional conditions, NC/Nga mice spontaneously develop an atopic dermatitis (AD)-like skin lesion accompanied by immunoglobulin E (IgE) hyperproduction and the expression of T helper 2 (Th2) cytokines. CpG DNA activates a strong interferon-gamma (IFN-gamma)-dominated T helper 1 (Th1) response, while inhibiting Th2-dependent allergies. In this study, we examined whether CpG oligodeoxynucleotide (ODN) could prevent the development of the skin lesions in NC/Nga mice. Sixteen of 26 NC/Nga mice did not exhibit dermatitis after CpG ODN was administered intraperitoneally every 2 wk for a total of five times. CpG ODN administration induced IFN-gamma production, which inhibited the production of Th2 cytokines (interleukin (IL)-4, IL-5, and IL-13) in both spleen and lymph node cells and culminated in a decrease in the serum IgE level. These data suggest that the CpG ODN has a therapeutic effect against AD; however, some mice (10 of 26) treated with CpG ODN exhibited an exacerbation of dermatitis accompanied by the hyperproduction of IFN-gamma, although Th2 cytokines were suppressed. These results suggest that the suppression of Th2 cytokines may not completely prevent dermatitis and that IFN-gamma may play a role in developing dermatitis in some NC/Nga mice.


Assuntos
Dermatite Atópica/genética , Dermatite Atópica/imunologia , Fosfatos de Dinucleosídeos , Imunoglobulina E/sangue , Interferon gama/imunologia , Oligodesoxirribonucleotídeos/farmacologia , Animais , Citocinas/imunologia , Dermatite Atópica/patologia , Dermatite Atópica/prevenção & controle , Modelos Animais de Doenças , Interferon gama/biossíntese , Linfócitos/imunologia , Camundongos , Camundongos Mutantes , Dermatopatias/imunologia , Dermatopatias/patologia , Baço/imunologia
7.
Vaccine ; 32(40): 5198-205, 2014 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-25066739

RESUMO

The gut-associated lymphoid tissue (GALT) represents a major reservoir of HIV in infected individuals. Vaccines can induce strong systemic immune responses but these have less impact on CD4 T cells activity and numbers in GALT. In this study, we vaccinated mice with an adenovirus vector that expressed the envelope gene from HIV and observed immune responses in the peripheral blood, spleen, liver, mesenteric lymph nodes, and Peyer's patches. We found that (1) the number of HIV-specific CD8 T cells was dramatically lower in GALT than in other tissues; (2) the programmed cell death protein-1 (PD-1) was expressed at high levels in HIV-specific CD8 T cells including memory T cells in GALT; and (3) high levels of HIV-specific CD8 T cell apoptosis were occurring in GALT. These results suggest that contributing to GALT becoming an HIV reservoir during infection is a combination of exhaustion and/or dysfunction of HIV-specific CTLs at that site. These results emphasize the importance of developing of an effective mucosal vaccine against HIV.


Assuntos
Apoptose/imunologia , Infecções por HIV/imunologia , Mucosa Intestinal/imunologia , Tecido Linfoide/imunologia , Linfócitos T Citotóxicos/imunologia , Animais , Linfócitos T CD8-Positivos/imunologia , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Receptor de Morte Celular Programada 1/metabolismo
8.
Nat Commun ; 5: 4978, 2014 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-25236377

RESUMO

Myeloid progenitors lose their potential to generate neutrophils when they adopt the mononuclear phagocyte lineage. The mechanism underlying this lineage restriction remains unknown. We here report that the protein expression of IRF8, an essential transcription factor for the development of dendritic cells (DCs) and monocytes, sharply increases at the monocyte-DC progenitor (MDP) stage and remains high in common monocyte progenitors (cMoPs). Irf8(-/-) MDPs and cMoPs accumulate but fail to efficiently generate their downstream populations, instead giving rise to neutrophils in vivo. IRF8 physically interacts with the transcription factor C/EBPα and prevents its binding to chromatin in MDPs and cMoPs, blocking the ability of C/EBPα to stimulate transcription and neutrophil differentiation. A partial inhibition of C/EBP activity in Irf8(-/-) haematopoietic progenitors alleviates the neutrophil overproduction in vivo. Thus, IRF8 not only bestows monocyte and DC differentiation potential upon mononuclear phagocyte progenitors but also restrains these progenitors from differentiating into neutrophils.


Assuntos
Proteína alfa Estimuladora de Ligação a CCAAT/antagonistas & inibidores , Regulação da Expressão Gênica , Fatores Reguladores de Interferon/metabolismo , Leucócitos Mononucleares/citologia , Neutrófilos/citologia , Fagócitos/citologia , Animais , Células da Medula Óssea/citologia , Diferenciação Celular , Cromatina/metabolismo , Feminino , Citometria de Fluxo , Genes Reporter , Células-Tronco Hematopoéticas/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco/citologia , Transcriptoma
9.
PLoS One ; 6(10): e25812, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22003407

RESUMO

Interferon regulatory factor (IRF) 8 and IRF4 are structurally-related, hematopoietic cell-specific transcription factors that cooperatively regulate the differentiation of dendritic cells and B cells. Whilst in myeloid cells IRF8 is known to modulate growth and differentiation, the role of IRF4 is poorly understood. In this study, we show that IRF4 has activities similar to IRF8 in regulating myeloid cell development. The ectopic expression of IRF4 in myeloid progenitor cells in vitro inhibits cell growth, promotes macrophages, but hinders granulocytic cell differentiation. We also show that IRF4 binds to and activates transcription through the IRF-Ets composite sequence (IECS). Furthermore, we demonstrate that Irf8⁻/⁻Irf4⁻/⁻ mice exhibit a more severe chronic myeloid leukemia (CML)-like disease than Irf8⁻/⁻ mice, involving a disproportionate expansion of granulocytes at the expense of monocytes/macrophages. Irf4⁻/⁻ mice, however, display no obvious abnormality in myeloid cell development, presumably because IRF4 is expressed at a much lower level than IRF8 in granulocyte-macrophage progenitors. Our results also suggest that IRF8 and IRF4 have not only common but also specific activities in myeloid cells. Since the expression of both the IRF8 and IRF4 genes is downregulated in CML patients, these results may add to our understanding of CML pathogenesis.


Assuntos
Fatores Reguladores de Interferon/metabolismo , Células Mieloides/citologia , Células Mieloides/metabolismo , Animais , Pontos de Checagem do Ciclo Celular , Diferenciação Celular , Proliferação de Células , DNA/genética , DNA/metabolismo , Regulação da Expressão Gênica , Humanos , Imunidade Inata , Fatores Reguladores de Interferon/deficiência , Fatores Reguladores de Interferon/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Macrófagos/citologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Células Mieloides/imunologia , Neutrófilos/citologia , Neutrófilos/imunologia , Neutrófilos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Especificidade por Substrato , Transcrição Gênica
10.
Vaccine ; 28(31): 4920-7, 2010 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-20566393

RESUMO

In this study, we explored the possibility of augmenting human immunodeficiency virus (HIV) gp120-specific cell-mediated immune responses in mice by means of a DNA vaccine encoding a mouse Ig Fcgamma2a fragment fused with gp120 (gp120-Ig, Ig-gp120). Western blotting analysis revealed that the HIV gp120 protein expression efficiency was higher in cells transfected with the gp120-Ig-coding plasmid (pGp120Ig) than in those transfected with the gp120 and Ig-gp120 expression plasmids (pGp120 and pIgGp120, respectively). pGp120Ig elicited more HIV-specific CD8 T cells and effector memory CD8 T cells than pGp120 in immunized mice. Furthermore, pGp120Ig significantly reduced the viral load after challenge with an HIV Env gp160-expressing vaccinia virus. These results demonstrate that covalent antigen modification with an Ig sequence can modulate antigen-specific cellular immune responses. The approach may be useful for vaccine development.


Assuntos
Vacinas contra a AIDS/imunologia , Proteína gp120 do Envelope de HIV/imunologia , Imunidade Celular , Vacinas de DNA/imunologia , Vacinas contra a AIDS/administração & dosagem , Vacinas contra a AIDS/genética , Animais , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular , Eletroporação , Feminino , Proteína gp120 do Envelope de HIV/genética , Infecções por HIV/imunologia , Infecções por HIV/prevenção & controle , Humanos , Injeções Intramusculares , Camundongos , Camundongos Endogâmicos BALB C , Plasmídeos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Vacinas de DNA/administração & dosagem , Vacinas de DNA/genética , Carga Viral
11.
Vaccine ; 25(19): 3809-15, 2007 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-17386962

RESUMO

Most of the recent HIV studies have focused on the clade B virus subtype. However, it is estimated that half the HIV patients in developing countries are infected with virus belonging to clade C. Therefore, a vaccine against HIV clade C is urgently required. In this study, we evaluate the immunogenicity and protective immunity of an adenovirus vector (Ad) in BALB/c mice and cynomolgus monkeys. We developed an HIV vaccine containing the HIV clade C gag gene using a replication-defective chimeric adenovirus type 5 (Ad5) vector incorporating Ad35 fiber (Ad5/35); this vector has exhibited low hepatotoxicity in animal models. We observed that immunization with the Ad5/35 vaccine generated heightened HIV-specific immune responses in both mice and monkeys. Furthermore, the Ad5/35 vector vaccine produced a cross-immunity against challenge with recombinant vaccinia viruses expressing HIV clade B gag. These results demonstrate that Ad5/35 vaccines expressing HIV clade C gag may be promising candidates for clinical trials.


Assuntos
Vacinas contra a AIDS , Adenovírus Humanos/genética , Genes gag/genética , Vetores Genéticos , Infecções por HIV/prevenção & controle , Proteínas Recombinantes de Fusão/metabolismo , Vacinas contra a AIDS/administração & dosagem , Vacinas contra a AIDS/genética , Vacinas contra a AIDS/imunologia , Animais , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Reações Cruzadas , Feminino , Produtos do Gene gag/genética , Produtos do Gene gag/imunologia , Produtos do Gene gag/metabolismo , Anticorpos Anti-HIV/sangue , Anticorpos Anti-HIV/imunologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , HIV-1/imunologia , Humanos , Macaca fascicularis , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Vaccinia virus
12.
J Virol ; 80(24): 11899-910, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17005662

RESUMO

The ability of adeno-associated virus serotype 1 to 8 (AAV1 to AAV8) vectors expressing the human immunodeficiency virus type 1 (HIV-1) Env gp160 (AAV-HIV) to induce an immune response was evaluated in BALB/c mice. The AAV5 vector showed a higher tropism for both mouse and human dendritic cells (DCs) than did the AAV2 vector, whereas other AAV serotype vectors transduced DCs only poorly. AAV1, AAV5, AAV7, and AAV8 were more highly expressed in muscle cells than AAV2. An immunogenicity study of AAV serotypes indicates that AAV1, AAV5, AAV7, and AAV8 vectors expressing the Env gp160 gene induced higher HIV-specific humoral and cell-mediated immune responses than the AAV2 vector did, with the AAV5 vector producing the best responses. Furthermore, mice injected with DCs that had been transduced ex vivo with an AAV5 vector expressing the gp160 gene elicited higher HIV-specific cell-mediated immune responses than did DCs transduced with AAV1 and AAV2 vectors. We also found that AAV vectors produced by HEK293 cells and insect cells elicit similar levels of antigen-specific immune responses. These results demonstrate that the immunogenicity of AAV vectors depends on their tropism for both antigen-presenting cells (such as DCs) and non-antigen-presenting cells (such as muscular cells) and that AAV5 is a better vector than other AAV serotypes. These results may aid in the development of AAV-based vaccine and gene therapy.


Assuntos
Células Dendríticas/imunologia , Dependovirus/imunologia , Vetores Genéticos/imunologia , HIV/imunologia , Transdução Genética/métodos , Animais , Western Blotting , Linhagem Celular , Células Dendríticas/virologia , Ensaio de Imunoadsorção Enzimática , Proteína gp160 do Envelope de HIV/imunologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , beta-Galactosidase/metabolismo
13.
J Autoimmun ; 24(3): 183-90, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15848040

RESUMO

Immunostimulatory CpG motifs can preferentially induce Th1 immune responses and have been applied to treat Th2-dominant disease. In this study, we investigated whether a plasmid with the addition of 20 copies of an immunostimulatory CpG motif (pB-CpG20) might prevent the development of scleroderma-like syndrome in tight-skin (Tsk/+) mice. Administration of pB-CpG20 to Tsk/+mice every 3 weeks starting at the age of 1 week reduced skin thickness and collagen content compared to that of pB or saline. The reduction was long lasting even after halting the treatment. Furthermore, this treatment partially reduced the production of anti-nuclear antibodies although it did not decrease the incidence of lung emphysema. pB-CpG20 increased the number of spleen cells secreting IFN-gamma and reduced that of the cells secreting IL-4 in vivo and in vitro compared to saline. These results suggest that repeated administration of a CpG-enriched plasmid can ameliorate scleroderma-like syndrome by biasing Th1 immunity in young Tsk/+mice.


Assuntos
Sequência Rica em GC/imunologia , Imunidade Celular/efeitos dos fármacos , Plasmídeos/administração & dosagem , Escleroderma Sistêmico/tratamento farmacológico , Células Th1/imunologia , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Transgênicos , Plasmídeos/genética , Plasmídeos/imunologia , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/patologia , Pele/imunologia , Pele/patologia , Células Th2/imunologia
14.
Vaccine ; 23(46-47): 5450-6, 2005 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-16006019

RESUMO

Adjuvants in vaccines are immune stimulants that play an important role in the induction of effective and appropriate immune responses to vaccine component(s). Diphtheria-tetanus-pertussis (DPT) vaccine contains not only aluminum hydrate (alum) to enhance the immune response to the vaccine ingredients, but also, both for that purpose and as a principal ingredient, pertussis toxin (PT). However, both adjuvants strongly promote T helper (Th) 2 type immune responses. Th1 and Th2 type immune responses are counterbalanced in vivo, and a Th2-prone immune response is not effective against intracellular infections but promotes IgE production, which is related to allergic disease. In this study, we used the CpG motif contained in oligodeoxynucleotide (CpG-ODN), which has an adjuvant effect and also induces the Th1 response, as an adjuvant to this vaccine, and we investigated its adjuvanticity and its potential to modulate immune responses to DPT vaccine. Administration of DPT vaccine with CpG-ODN (DPT-alum/ODN) to mice significantly reduced the total IgE levels and increased the anti-PT specific IgG2a titer in serum, in comparison with ordinary DPT vaccine (DPT-alum). Moreover, we investigated the antibody response to orally administrated ovalbumin (OVA) after vaccine administration. In the DPT-alum/ODN-administered group, the OVA specific IgE production in serum greatly decreased in comparison with that in the DPT-alum-administered group. These data indicate that CpG-ODN was not useful only as an efficient vaccine adjuvant but also shifted the immune responses substantially toward Th1 and modulated the Th1/Th2 immune response in DPT vaccine. These data suggested new applications of CpG-ODN as adjuvants in DPT vaccine.


Assuntos
Adjuvantes Imunológicos/farmacologia , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Imunidade Celular/efeitos dos fármacos , Oligonucleotídeos/farmacologia , Células Th1/imunologia , Células Th2/imunologia , Compostos de Alúmen/farmacologia , Animais , Antígenos/administração & dosagem , Antígenos/imunologia , Ilhas de CpG , Ensaio de Imunoadsorção Enzimática , Feminino , Hipersensibilidade/prevenção & controle , Imunoglobulina G/análise , Imunoglobulina G/biossíntese , Intubação Gastrointestinal , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA