Allergen-specific Th1 cells fail to counterbalance Th2 cell-induced airway hyperreactivity but cause severe airway inflammation
Allergen-specific Th1 cells fail to counterbalance Th2 cell-induced airway hyperreactivity but cause severe airway inflammation
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DOI：
10.1172/jci5155
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发表时间：
1999-01-01
影响因子：
15.9
通讯作者：
Umetsu, DT
中科院分区：
文献类型：
--
作者：
Hansen, G;Berry, G;Umetsu, DT
在工业化国家中多达10%的个体中存在过敏性哮喘，其特征在于由分泌白细胞介素-4（IL-4）和IL-5的过敏原特异性Th 2细胞诱导的慢性气道炎症和高反应性。由于Th 1细胞拮抗Th 2细胞功能，因此已经提出向Th 1的免疫偏离可以防止哮喘和过敏。使用过继转移系统，我们评估了Th 1，Th 2和Th 0细胞在哮喘小鼠模型中的作用，并检查了Th 1细胞抵消Th 2细胞促哮喘作用的能力。从卵清蛋白（OVA）特异性T细胞受体（TCR）转基因小鼠中产生Th 1、Th 2和Th 0细胞系，并将其转移到淋巴细胞缺陷、OVA治疗的严重联合免疫缺陷（SCID）小鼠中。OVA特异性Th 2和Th 0细胞诱导显著的气道高反应性和炎症。令人惊讶的是，在SCID小鼠或OVA免疫的免疫活性BALB/c小鼠中，Th 1细胞没有减弱Th 2细胞诱导的气道高反应性和炎症，而是引起严重的气道炎症。这些结果表明，抗原特异性Th 1细胞可能不会保护或预防Th 2介导的过敏性疾病，而是可能导致急性肺病理。这些发现对哮喘和过敏的当前治疗目标具有重要意义，并表明Th 2主导的过敏性炎症反应转化为Th 1主导的反应可能导致进一步的问题。
Allergic asthma, which is present in as many as 10% of individuals in industrialized nations, is characterized by chronic airway inflammation and hyperreactivity induced by allergen-specific Th2 cells secreting interleukin-4 (IL-4) and IL-5. Because Th1 cells antagonize Th2 cell functions, it has been proposed that immune deviation toward Th1 can protect against asthma and allergies. Using an adoptive transfer system, we assessed the roles of Th1, Th2, and Th0 cells in a mouse model of asthma and examined the capacity of Th1 cells to counterbalance the proasthmatic effects of Th2 cells. Th1, Th2, and Th0 lines were generated from ovalbumin (OVA)-specific T-cell receptor (TCR) transgenic mice and transferred into lymphocyte-deficient, OVA-treated severe combined immunodeficiency (SCID) mice. OVA-specific Th2 and Th0 cells induced significant airway hyperreactivity and inflammation. Surprisingly, Th1 cells did not attenuate Th2 cell-induced airway hyperreactivity and inflammation in either SCID mice or in OVA-immunized immunocompetent BALB/c mice, but rather caused severe airway inflammation. These results indicate that antigen-specific Th1 cells may not protect or prevent Th2-mediated allergic disease, but rather may cause acute lung pathology. These findings have significant implications with regard to current therapeutic goals in asthma and allergy and suggest that conversion of Th2-dominated allergic inflammatory responses into Th1-dominated responses may lead to further problems.