Mearns Helen, Horsnell William G C, Hoving J Claire, Dewals Benjamin, Cutler Antony J, Kirstein Frank, Myburgh Elmarie, Arendse Berenice, Brombacher Frank
International Centre for Genetic Engineering and Biotechnology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Infect Immun. 2008 Dec;76(12):5535-42. doi: 10.1128/IAI.00210-08. Epub 2008 Sep 22.
The role of CD4(+) T-cell interleukin-4 (IL-4) receptor alpha (IL-4Ralpha) expression in T helper 2 (TH2) immune responses has not been defined. To examine this role, we infected CD4(+) T-cell IL-4Ralpha knockout (KO) mice with the parasitic nematode Nippostrongylus brasiliensis, which induces strong host TH2 responses. Although N. brasiliensis expulsion was not affected in CD4(+) T-cell IL-4Ralpha KO mice, the associated lung pathology was reduced. Infected CD4(+) T-cell IL-4Ralpha KO mice showed abrogation of airway mucus production. Furthermore, CD4(+) T-cell IL-4Ralpha KO mouse lungs contained reduced numbers of lymphocytes and eosinophils. Restimulation of pulmonary region-associated T-cell populations showed that TH2 cytokine responses were disrupted. Secretion of IL-4, but not secretion of IL-13 or IL-5, from mediastinal lymph node CD4(+) T cells was reduced in infected CD4(+) T-cell IL-4Ralpha KO mice. Restimulation of tissue-derived CD4(+) T cells resulted in equivalent levels of IL-4 and IL-13 on day 7 postinfection (p.i.) in control and CD4(+) T-cell IL-4Ralpha KO mice. By day 10 p.i. the TH2 cytokine levels had significantly declined in CD4(+) T-cell IL-4Ralpha KO mice. Restimulation with N. brasiliensis antigen of total lung cell populations and populations with CD4(+) T cells depleted showed that CD4(+) T cells were a key TH2 cytokine source. These data demonstrated that CD4(+) T-cell IL-4 responsiveness facilitates eosinophil and lymphocyte recruitment, lymphocyte localization, and TH2 cytokine production in the allergic pathology associated with N. brasiliensis infections.
CD4(+) T细胞白细胞介素-4（IL-4）受体α（IL-4Rα）表达在辅助性T细胞2（TH2）免疫反应中的作用尚未明确。为研究此作用，我们用巴西日圆线虫感染CD4(+) T细胞IL-4Rα基因敲除（KO）小鼠，该线虫可诱导强烈的宿主TH2反应。尽管在CD4(+) T细胞IL-4Rα KO小鼠中巴西日圆线虫的排出未受影响，但相关的肺部病理变化减轻。感染的CD4(+) T细胞IL-4Rα KO小鼠显示气道黏液分泌减少。此外，CD4(+) T细胞IL-4Rα KO小鼠肺中淋巴细胞和嗜酸性粒细胞数量减少。对肺区域相关T细胞群体的再刺激表明TH2细胞因子反应受到破坏。在感染的CD4(+) T细胞IL-4Rα KO小鼠中，纵隔淋巴结CD4(+) T细胞分泌IL-4，但不分泌IL-13或IL-5。在感染后第7天（p.i.），对照小鼠和CD4(+) T细胞IL-4Rα KO小鼠中组织来源的CD4(+) T细胞再刺激产生的IL-4和IL-13水平相当。到感染后第10天，CD4(+) T细胞IL-4Rα KO小鼠中的TH2细胞因子水平显著下降。用巴西日圆线虫抗原对全肺细胞群体以及耗尽CD4(+) T细胞的群体进行再刺激表明，CD4(+) T细胞是关键的TH2细胞因子来源。这些数据表明，CD4(+) T细胞对IL-4的反应性促进了嗜酸性粒细胞和淋巴细胞的募集、淋巴细胞定位以及与巴西日圆线虫感染相关的过敏性病理中的TH2细胞因子产生。
