Beta 2-microglobulin-dependent T cells are dispensable for allergen-induced T helper 2 responses.
Beta 2-microglobulin-dependent T cells are dispensable for allergen-induced T helper 2 responses.
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β2-微球蛋白依赖性T细胞对于过敏原诱导的T辅助2反应可分配。
DOI：
10.1084/jem.184.4.1507
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发表时间：
1996-10-01
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T辅助细胞（Th）2表型的CD 4+和CD 8 + α/β + T细胞产生促进IgE产生和嗜酸性粒细胞性炎症的细胞因子IL-4、IL-5和IL-13。IL-4可能在介导抗原初始α/β + T细胞分化为Th 2细胞中起重要作用。鼠NK1.1+（CD 4+或CD 4-CD 8-）α/β + T细胞包含β 2-微球蛋白（β 2 m）依赖性细胞群，其在体外和体内细胞活化后快速产生IL-4，并且已被提出作为用于Th 2细胞分化的IL-4来源。α/β + CD 8 + T细胞（其中大多数需要β 2 m用于其发育）也被提出作为过敏原诱导的Th 2应答的正调节剂。我们通过用卵清蛋白（OVA）治疗野生型、β 2 m缺陷型（β 2 m-/-）和IL-4缺陷型（IL-4 -/-）C57 BL/6遗传背景小鼠，使用在野生型小鼠中诱导强烈过敏性肺病的方案，测试β 2 m依赖性T细胞是否是Th 2细胞介导的过敏反应所必需的。OVA处理的β 2 m-/-小鼠的总IgE和OVA特异性IgE、肺嗜酸性粒细胞增多症的循环水平以及支气管淋巴结组织中IL-4、IL-5和IL-13 mRNA的表达与OVA处理的野生型小鼠相似。相反，与野生型小鼠相比，OVA处理的IL-4 -/-小鼠中的这些反应全部不可检测或显著降低，证实了IL-4在该过敏模型中是必需的。这些结果表明，NK 1.1 + α/β + T细胞群体以及其他β 2 m依赖性群体，如大多数外周α/β + CD 8 + T细胞，对于Th 2肺部对蛋白过敏原的应答是不利的。
CD4+ and CD8+ alpha/beta+ T cells of the T helper cell (Th)2 phenotype produce the cytokines IL-4, IL-5, and IL-13 that promote IgE production and eosinophilic inflammation. IL-4 may play an important role in mediating the differentiation of antigenically naive alpha/beta+ T cells into Th2 cells. Murine NK1.1+ (CD4+ or CD4-CD8-) alpha/beta+ T cells comprise a beta 2-microglobulin (beta 2m)-dependent cell population that rapidly produces IL-4 after cell activation in vitro and in vivo and has been proposed as a source of IL-4 for Th2 cell differentiation. alpha/beta+ CD8+ T cells, most of which require beta 2m for their development, have also been proposed as positive regulators of allergen-induced Th2 responses. We tested whether beta 2m- dependent T cells were essential for Th2 cell-mediated allergic reactions by treating wild-type, beta 2m-deficient (beta 2m -/-), and IL-4-deficient (IL-4 -/-) mice of the C57BL/6 genetic background with ovalbumin (OVA), using a protocol that induces robust allergic pulmonary disease in wild-type mice. OVA-treated beta 2m -/- mice had circulating levels of total and OVA-specific IgE, pulmonary eosinophilia, and expression of IL-4, IL-5, and IL-13 mRNA in bronchial lymph node tissue similar to that of OVA-treated wild-type mice. In contrast, these responses in OVA-treated IL-4 -/- mice were all either undetectable or markedly reduced compared with wild-type mice, confirming that IL-4 was required in this allergic model. These results indicate that the NK1.1+ alpha/beta+ T cell population, as well as other beta 2m-dependent populations, such as most peripheral alpha/beta+ CD8+ T cells, are dispensable for the Th2 pulmonary response to protein allergens.