Haselden B M, Syrigou E, Jones M, Huston D, Ichikawa K, Chapman M D, Kay A B, Larché M
Department of Allergy and Clinical Immunology, Imperial College School of Medicine at the National Heart and Lung Institute, London, United Kingdom.
J Allergy Clin Immunol. 2001 Sep;108(3):349-56. doi: 10.1067/mai.2001.117461.
In general, T cells from normal, nonatopic individuals respond to aeroallergens with synthesis and release of IFN-gamma. In contrast, release of T(H)2-type cytokines by activated lymphocytes is a feature of allergic rhinitis and atopic asthma.
The purpose of this study was to determine differences in T-cell recognition of epitopes within allergenic sequences, in terms of proliferation and cytokine production, in subjects with atopic asthma compared with subjects with allergic rhinitis and normal controls.
Proliferative responses and IL-5/IFN-gamma release patterns from PBMCs from cat-allergic asthmatic, cat-allergic rhinitic, and non-cat-allergic asthmatic subjects and nonatopic normal controls were determined in primary cultures. Cells were challenged with 7 overlapping peptides spanning chain 1 of the major cat allergen, Fel d 1.
The 4 groups did not differ with respect to the ability to mount proliferative responses to Fel d 1 peptides. In all groups, the IFN-gamma responses were predominantly to the amino terminus peptides. Cat-allergic and non-cat-allergic asthmatic subjects (and not cat-allergic rhinitic subjects and normal controls) made IL-5 responses to most of the Fel d 1 peptides, the result being a mixed (T(H)0) cytokine response at the N-terminus and a restricted (T(H)2) response at the C-terminus.
Proliferative and IL-5/IFN-gamma responses of T cells from asthmatic and atopic rhinitic subjects and normal controls to allergen peptides can be dissociated. Furthermore, differing cytokine responses to peptides derived from a single antigen suggest that certain domains of the molecule might preferentially induce IL-5 rather than IFN-gamma and as a result could be more important in disease pathogenesis.
一般来说,来自正常、非特应性个体的T细胞会通过合成和释放γ干扰素来对气传变应原作出反应。相比之下,活化淋巴细胞释放2型辅助性T细胞(TH2)细胞因子是变应性鼻炎和特应性哮喘的一个特征。
本研究的目的是确定与变应性鼻炎患者和正常对照相比,特应性哮喘患者的T细胞在增殖和细胞因子产生方面对变应原序列内表位的识别差异。
在原代培养中测定来自猫变应性哮喘患者、猫变应性鼻炎患者、非猫变应性哮喘患者和非特应性正常对照的外周血单核细胞(PBMC)的增殖反应以及白细胞介素-5(IL-5)/γ干扰素(IFN-γ)释放模式。用跨越主要猫变应原Fel d 1链1的7个重叠肽刺激细胞。
四组在对Fel d 1肽产生增殖反应的能力方面没有差异。在所有组中,IFN-γ反应主要针对氨基末端肽。猫变应性和非猫变应性哮喘患者(而非猫变应性鼻炎患者和正常对照)对大多数Fel d 1肽产生IL-5反应,结果是在N末端出现混合(TH0)细胞因子反应,在C末端出现受限(TH2)反应。
哮喘患者、变应性鼻炎患者和正常对照的T细胞对变应原肽的增殖反应以及IL-5/IFN-γ反应可能是分离的。此外,对源自单一抗原的肽的不同细胞因子反应表明,该分子的某些结构域可能优先诱导IL-5而非IFN-γ,因此在疾病发病机制中可能更重要。