Subcutaneous Vaccination of Mycobacterium bovis Bacillus Calmette-Guérin Attenuates Allergic Inflammation in a Murine Model of Asthma

Subcutaneous Vaccination of Mycobacterium bovis Bacillus Calmette-Guérin Attenuates Allergic Inflammation in a Murine Model of Asthma
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皮下接种牛分枝杆菌卡介苗可减轻哮喘小鼠模型中的过敏性炎症

DOI:
10.2332/allergolint.54.601
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发表时间:
2005
影响因子:
6.8
通讯作者:
E. Kita
E. Kita
中科院分区:
医学2区
文献类型:
--
作者:
Toshihiro Ito;K. Hamada;Yasue Suzaki;H. Kimura;N. Matsui;E. Kita

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背景:过敏性疾病发病率的增加,尤其是在发达国家,可以用卫生假说来解释。已经研究了一种在 Th2 偏向免疫条件下引起 Th1 主导反应的新治疗方法。牛分枝杆菌卡介苗 (BCG) 是一种广泛使用的抗结核疫苗,可强烈诱导以 Th1 为主的免疫反应。据报道,卡介苗在治疗过敏性疾病中具有潜在作用。在本研究中,我们研究了皮下接种低剂量(1×105)卡介苗疫苗是否可以减轻哮喘小鼠模型中的气道过敏性炎症。方法:雌性 BALB c 小鼠在第 0 天皮下注射疫苗。分别在第7天和第14天注射1×10 5 CFU的BCG,并对卵清蛋白(OVA,腹腔注射,含明矾)致敏。间隔两周后,他们接触雾化 OVA (1%)。在另一项实验中,BCG 致敏的脾 CD4+ T 细胞在致敏前进行过继转移。结果:我们发现接种卡介苗的小鼠 BALF 中嗜酸性粒细胞较少,过敏性炎症也较轻。接种疫苗的小鼠中IL-4以及Eotaxin和TARC的表达下调,而IL-12和IFN-γ的表达上调。此外,在 OVA 致敏之前将接种小鼠的脾 CD4 + T 细胞转移到未接种小鼠体内可防止过敏性炎症的发生。这些脾脏 CD4+ T 细胞产生大量 IFN-γ。结论:皮下注射(低剂量)BCG 疫苗可通过 Th1 偏向免疫抑制过敏性炎症,并可能在哮喘免疫治疗中具有临床应用。
Background: The increase in the incidence of allergic disorders especially in developed countries may be ex- plained by the hygiene hypothesis. A novel therapeutic approach that causes a Th1-dominant response under conditions of Th2-skewed immunity has been investigated. Mycobacterium bovis Bacillus Calmette-Gurin (BCG) is a widely used anti-tuberculosis vaccine that strongly induces a Th1-predominant immune response. A potential role for BCG in the treatment of allergic diseases has been reported. In the present study, we investi- gated whether subcutaneous inoculation with a low dose (1 × 105) of BCG vaccine can attenuate allergic in- flammation of the airway in a murine model of asthma. Methods: Female BALB c mice were vaccinated on day 0 with a subcutaneous. injection of 1 × 10 5 CFU of BCG, and sensitized to ovalbumin (OVA, i.p., with alum) on day 7 and 14, respectively. After a 2-week interval, they were exposed to aerosolized OVA (1%). In another experiment, BCG-sensitized splenic CD4+ T cells were adoptively transferred before sensitization. Results: We found that BCG-vaccinated mice had fewer eosinophils in BALF and less severe allergic inflam- mation. The expression of IL-4 as well as Eotaxin and TARC was down-regulated in the vaccinated mice, while that of both IL-12 and IFN-γ was up-regulated. Moreover, the transfer of splenic CD4 + T cells from vaccinated mice into nave mice before OVA-sensitization prevented the development of allergic inflammation. These splenic CD4+ T cells produced much IFN-γ. Conclusions: The subcutaneous administration of (low-dose) BCG vaccine suppressed allergic inflammation via Th1-skewed immunity and might have clinical applications in immunotherapy for asthma.
儿童哮喘的进展:卫生假说、自然史和治疗。
DOI: 10.1067/mai.2003.148
发表时间: 2003
期刊: The Journal of allergy and clinical immunology
影响因子: --
作者:
Liu,AndrewH;Szefler,StanleyJ
通讯作者: Szefler,StanleyJ
DOI: 10.1056/nejm200008243430803
发表时间: 2000-08-24
影响因子: 158.5
作者:
Ball, TM;Castro-Rodriguez, JA;Wright, AL
通讯作者: Wright, AL
DOI: 10.1086/515614
发表时间: 1998
期刊: The Journal of infectious diseases
影响因子: --
作者:
Lowry,PW;Ludwig,TS;Adams,JA;Fitzpatrick,ML;Grant,SM;Andrle,GA;Offerdahl,MR;Cho,SN;JacobsJr,DR
通讯作者: JacobsJr,DR