Autophagy deficiency in myeloid cells exacerbates eosinophilic inflammation in chronic rhinosinusitis

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Basophils initiate IL-4 production during a memory T-dependent response

Experiments were performed to characterize and identify the cellular sources of the secondary interleukin (IL)-4 response to a T cell-dependent antigen. Mice were primed by immunization with goat anti-mouse immunoglobulin (Ig)D antibody (GaMD), which stimulates naive CD4+ T cells to secrete IL-4 in 3-4 d. When challenged with goat serum 14 d after immunization, GaMD-primed mice generated an IL-4 response that exceeded the primary response by approximately 100-fold, started in <2 h, and lasted for 4 d. Studies with 4get mice, in which cells with an accessible Il4 gene express a green fluorescent protein (GFP), revealed CD4+ memory T cells, natural killer T cells, basophils, mast cells, and eosinophils as possible rapid producers of IL-4. GFP(+)CD4+ T cells and basophils expanded more in the spleen than the other cell types during the primary response to GaMD. Quantitation of in vivo IL-4 production by the in vivo cytokine capture assay after individual cell types were selectively stimulated or deleted demonstrated that basophils and memory CD4+ T cells account for most of the secondary IL-4 response, with basophils initiating that response through IgE/FcepsilonRI-mediated signaling but secreting IL-4 for <4 h and memory T cells secreting IL-4 within 4 h and continuing to secrete this cytokine for 4 d.     

哮喘患儿体内EOS、IgE、IL-4及IFN-γ水平的检测及临床意义

目的：探讨哮喘患儿体内嗜酸性粒细胞(eosinophil,EOS)、免疫球蛋白E(IgE)、白介素4(IL-4)及γ干扰素(IFN-γ)水平的检测及临床意义,为临床疾病的诊断和治疗提供依据。方法抽选湖北省鄂州市鄂钢医院2012年11月至2013年6月收治的95例哮喘患儿(哮喘组,其中急性发作期47例、缓解期48例),并抽选同期在本院体检的79例健康患者为对照研究(健康组),采用肺功能仪测定两组的肺功能,并采用痰液诱导、酶联免疫吸附法( ELISA)分别测定患儿痰液中的EOS百分率及血清中IgE、IL-4、IFN-γ水平。结果哮喘组患儿的1秒用力呼气容积(FEV1)/用力肺活量(FVC)的比值(FEV1%)为(69.67±6.63)%,明显低于健康组的(102.27±11.93)%,差异具有统计学意义(t=22.750,P<0.001);哮喘组患儿的FEV1占预计值百分比为(70.45±9.62),明显低于健康组的(90.13±6.34),差异有统计学意义(t=15.582,P<0.001)。哮喘组患儿的痰EOS百分率、血清中IgE、IL-4水平均高于健康组(t值分别为321.962、82.644、76.913,均P<0.05),哮喘组患儿的IFN-γ水平明显低于健康组(t=30.207,P<0.001)。急性发作期哮喘患儿的痰EOS百分率及血清中IgE、IL-4水平均高于缓解期哮喘患儿的(t值分别为15.752、40.762、31.162,均P<0.05),急性发作期哮喘患儿的IFN-γ水平明显低于缓解期哮喘患儿的(t=35.892,P<0.05)。结论血清中IL-4、IgE水平及痰液中EOS百分率升高、血清IFN-γ水平降低,与哮喘的发生、发展密切相关,对其治疗及病情判断具有重要价值。