IL-10 and TGF-β cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy

IL-10 and TGF-β cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy
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DOI:
10.1002/eji.200322919
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发表时间:
2003-05-01
影响因子:
5.4
通讯作者:
Akdis, CA
Akdis, CA
中科院分区:
医学3区
文献类型:
--
作者:
Jutel, M;Akdis, M;Akdis, CA

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对粘膜中空气传播的过敏原的正常和过敏性免疫应答的调节仍然知之甚少,特异性免疫疗法(SIT)使对这些过敏原的过敏应答正常化的机制目前尚不清楚。因此,我们研究了免疫调节机制的正常和过敏反应的主要屋尘螨(HDM)和桦树花粉过敏原- Dermatophagoides pteroynyssinus(Derp)1和Bet V 1,分别-以及免疫基础的SIT HDM鼻炎和哮喘患者。在HDM和桦树花粉的正常免疫中,观察到变应原特异性外周T细胞对Der p 1和Bet v 1的抑制。偏离的免疫应答的特征在于抑制增殖性T细胞和Th 1(IFN-γ)和Th 2(IL-5、IL-13)细胞因子应答,以及增加过敏原特异性T细胞的IL-10和TGF-β分泌。细胞因子活性的中和表明,在SIT期间和对粘膜过敏原的正常免疫中,IL-10和TGF-β诱导T细胞抑制。此外,SIT在过敏个体的CD 4(+)CD 25(+)T细胞中诱导抗原特异性抑制活性。总之,这些结果表明,在SIT期间和正常免疫中,作为对粘膜抗原的健康免疫应答的关键事件,向调节/抑制T细胞应答的偏离。
The regulation of normal and allergic immune responses to airborne allergens in the mucosa is still poorly understood, and the mechanism of specific immunotherapy (SIT) in normalizing the allergic response to such allergens is currently not clear. Accordingly, we have investigated the immunoregulatory mechanism of both normal and allergic responses to the major house-dust mite (HDM) and birch pollen allergens - Dermatophagoides pteroynyssinus (Der p)1 and Bet v 1, respectively - as well as the immunologic basis of SIT to HDM in rhinitis and asthma patients. In normal immunity to HDM and birch pollen, an allergen-specific peripheral T cell suppression to Der p 1 and Bet v 1 was observed. The deviated immune response was characterized by suppressed proliferative T cell and Th1 (IFN-gamma) and Th2 (IL-5, IL-13) cytokine responses, and increased IL-10 and TGF-beta secretion by allergen-specific T cells. Neutralization of cytokine activity showed that T cell suppression was induced by IL-10 and TGF-beta during SIT and in normal immunity to the mucosal allergens. In addition, SIT induced an antigen-specific suppressive activity in CD4(+) CD25(+) T cells of allergic individuals. Together, these results demonstrate a deviation towards a regulatory/suppressor T cell response during SIT and in normal immunity as a key event for the healthy immune response to mucosal antigens.