Garfias Y, Ortiz B, Hernández J, Magaña D, Becerril-Angeles M, Zenteno E, Lascurain R
Instituto de Oftalmología, Fundación Conde de Valenciana, Mexico.
Allergy. 2006 Jan;61(1):27-34. doi: 10.1111/j.1398-9995.2005.00951.x.
Airway allergic diseases are regulated by interleukin (IL)-5, which causes infiltration of eosinophils into the bronchial epithelium, and by IL-4 which increases serum immunoglobulin E (IgE) production and promotes CD30 expression on Th cells. CD30 generates a costimulatory signal involved in apoptosis or cell proliferation, depending on the microenvironment. Our aims were: (i) to analyze if CD4+ CD30+ T cells from allergic patients proliferate in response to Dermatophagoides pteronyssinus, and (ii) if upon stimulation this cell population produces IL-4 and IL-5.
Peripheral blood mononuclear cell (PBMC) from 17 allergic rhinitis and mild allergic asthma patients and 12 healthy nonallergic individuals were stimulated with allergen in the presence or absence of anti-IL-4, anti-IL-5 or anti-IL-4Ralpha monoclonal antibodies (mAbs). TdT-mediated dUTP nick end-labeling (TUNEL) assay, 7-aminoactinomycin-D (7-AAD) intercalation, and flow cytometry were used to determine the CD4+ CD30+ blasts percentage, cell proliferation, apoptosis, and intracellular cytokines after 7 culture days.
Cell proliferation induced with allergen showed that 90% of the allergen-stimulated blasts were CD4+, 50% of which were CD30+. Allergen-stimulated PBMC showed a progressive increase (mean: from 7% to 23%) of CD4+ CD30+IFN-gamma+ and CD4+ CD30+IL-4+ blasts which diminished (mean: 6%) after 5 culture days. In contrast, CD4+ CD30+IL-5+ blasts showed a continuous progression (from 12% to 24%) that maintained after 7 culture days. The vast majority of CD4+ CD30+ blasts were negative to 7-AAD or TUNEL. Additionally, a significant decrease (34%) was observed in the number of CD4+ CD30+ blasts when IL-4 was neutralized.
These data suggest that specific allergen stimulation of PBMC isolated from allergic patients generates a nonapoptotic CD4+ CD30+ blast subset that produces IL-5.
气道过敏性疾病受白细胞介素（IL）-5调节，IL-5可导致嗜酸性粒细胞浸润至支气管上皮，还受IL-4调节，IL-4可增加血清免疫球蛋白E（IgE）的产生并促进Th细胞上CD30的表达。CD30会产生一种共刺激信号，该信号根据微环境参与细胞凋亡或细胞增殖。我们的目的是：（i）分析来自过敏患者的CD4+ CD30+ T细胞是否会对尘螨产生增殖反应，以及（ii）该细胞群体在受到刺激后是否会产生IL-4和IL-5。
在有或没有抗IL-4、抗IL-5或抗IL-4Rα单克隆抗体（mAb）存在的情况下，用变应原刺激17例过敏性鼻炎和轻度过敏性哮喘患者以及12名健康非过敏个体的外周血单个核细胞（PBMC）。培养7天后，采用TdT介导的dUTP缺口末端标记（TUNEL）测定法、7-氨基放线菌素-D（7-AAD）嵌入法和流式细胞术来确定CD4+ CD30+母细胞百分比、细胞增殖、细胞凋亡和细胞内细胞因子。
变应原诱导的细胞增殖表明，90%的变应原刺激母细胞为CD4+，其中50%为CD30+。变应原刺激的PBMC显示，CD4+ CD30+IFN-γ+和CD4+ CD30+IL-4+母细胞逐渐增加（平均：从7%增至23%），在培养5天后减少（平均：6%）。相比之下，CD4+ CD30+IL-5+母细胞呈持续增加（从12%增至24%），并在培养7天后维持该水平。绝大多数CD4+ CD30+母细胞对7-AAD或TUNEL呈阴性。此外，当IL-4被中和时，观察到CD4+ CD30+母细胞数量显著减少（34%）。
这些数据表明，从过敏患者分离的PBMC经特异性变应原刺激后会产生一个非凋亡性的产生IL-5的CD4+ CD30+母细胞亚群。
