Lung and Allergy Research Centre, School of Medicine, The University of Queensland, Princess Alexandra Hospital, Buranda, Brisbane, Australia.
Immunol Cell Biol. 2012 Nov;90(10):974-7. doi: 10.1038/icb.2012.39. Epub 2012 Jul 24.
Several studies provided evidence of innate interferons (IFNs) regulating T(H)2 cytokine production using purified CD4(+) memory cells and T(H)2 polarisation via interleukin-4 (IL-4). Vitally, none of these previous studies examined IFN attenuation of T(H)2 responses to allergen or antigen. This study therefore sought to investigate the abrogation of specific allergen- and antigen-stimulated T(H)2 response in peripheral blood mononuclear cells (PBMC) derived from 12 sensitised individuals by IFN-β and IFN-λ. PBMC were cultured in the presence of house dust mite (HDM) allergen, rhinovirus (RV), influenza vaccine and tetanus toxoid (TT)±either IFN-β or IFN-λ for 3 and 5 days. IFN-γ, IL-5 and IL-13 protein levels were measured by ELISA. Quantitative PCR (qPCR) was used to investigate induction of genes involved in control of T(H)2 cytokines. No alteration in T(H)1 IFN-γ allergen/antigen response was observed with addition of IFN-β or IFN-λ. Consistent abrogation of T(H)2 response to HDM and influenza was observed with IFN-β at both time points; attenuation was observed by day 5 with RV and TT. IFN-λ had no consistent effect on T(H)2 production except in the presence of RV (multiplicity of infection=5); a decrease in IL-5 alone was observed in the presence of trivalent inactivated influenza vaccine. GATA binding protein 3 (GATA3) and suppressors of cytokine signalling3 mRNA were differentially regulated in HDM and influenza-stimulated cultures±IFN-β. We concluded that IFN-β produced a strong and consistent abrogation of T(H)2 cytokine production in the presence of a range of allergen and antigen stimulants.
几项研究利用纯化的 CD4+记忆细胞和白细胞介素-4（IL-4）提供了先天干扰素（IFN）调节 T(H)2 细胞因子产生的证据。至关重要的是，这些之前的研究都没有检查 IFN 对过敏原或抗原的 T(H)2 反应的抑制作用。因此，本研究旨在研究 IFN-β 和 IFN-λ 对 12 名致敏个体来源的外周血单个核细胞（PBMC）中特定过敏原和抗原刺激的 T(H)2 反应的阻断作用。将 PBMC 在屋尘螨（HDM）过敏原、鼻病毒（RV）、流感疫苗和破伤风类毒素（TT）存在的情况下培养 3 和 5 天±IFN-β 或 IFN-λ。通过 ELISA 测量 IFN-γ、IL-5 和 IL-13 蛋白水平。使用定量 PCR（qPCR）来研究参与控制 T(H)2 细胞因子的基因的诱导。添加 IFN-β 或 IFN-λ不会改变 T(H)1 IFN-γ 过敏原/抗原反应。IFN-β 在两个时间点均一致阻断对 HDM 和流感的 T(H)2 反应；在 RV 和 TT 存在的情况下，在第 5 天观察到衰减。IFN-λ 对 T(H)2 产生没有一致的影响，除了在 RV 存在的情况下（感染倍数=5）；在三价灭活流感疫苗存在的情况下，仅观察到 IL-5 的减少。在 HDM 和流感刺激培养物中，GATA 结合蛋白 3（GATA3）和细胞因子信号转导抑制剂 3（SOCS3）mRNA 的表达受到差异调控±IFN-β。我们得出结论，IFN-β 在存在多种过敏原和抗原刺激物的情况下产生了强烈且一致的 T(H)2 细胞因子产生的阻断作用。
