Department of Parasitology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands; Current address: Department of Internal Medicine-Rheumatology, University of Michigan Medical School, 109 Zina Pitcher Place, Ann Arbor, MI, USA.
Department of Parasitology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
Int J Parasitol. 2017 Aug;47(9):545-554. doi: 10.1016/j.ijpara.2017.02.002. Epub 2017 Apr 4.
Chronic schistosome infections protect against allergic airway inflammation (AAI) via the induction of IL-10-producing splenic regulatory B (Breg) cells. Previous experiments have demonstrated that schistosome-induced pulmonary B cells can also reduce AAI, but act independently of IL-10. We have now further characterized the phenotype and inhibitory activity of these protective pulmonary B cells. We excluded a role for regulatory T (Treg) cell induction as putative AAI-protective mechanisms. Schistosome-induced B cells showed increased CD86 expression and reduced cytokine expression in response to Toll-like receptor (TLR) ligands compared with control B cells. To investigate the consequences for T cell activation we cultured ovalbumin (OVA)-pulsed, schistosome-induced B cells with OVA-specific transgenic T cells and observed less Th2 cytokine expression and T cell proliferation compared with control conditions. This suppressive effect was preserved even under optimal T cell stimulation by anti-CD3/28. Blocking of the inhibitory cytokines IL-10 or TGF-β only marginally restored Th2 cytokine induction. These data suggest that schistosome-induced pulmonary B cells are impaired in their capacity to produce cytokines to TLR ligands and to induce Th2 cytokine responses independent of their antigen-presenting function. These findings underline the presence of distinct B cell subsets with different stimulatory or inhibitory properties even if induced by the same type of helminth.
慢性血吸虫感染通过诱导产生 IL-10 的脾调节性 B（Breg）细胞来预防过敏性气道炎症（AAI）。先前的实验表明，血吸虫诱导的肺 B 细胞也可以减少 AAI，但与 IL-10 无关。我们现在进一步描述了这些保护性肺 B 细胞的表型和抑制活性。我们排除了调节性 T（Treg）细胞诱导作为潜在的 AAI 保护机制的作用。与对照 B 细胞相比，血吸虫诱导的 B 细胞在 TLR 配体刺激下表达增加的 CD86 和减少的细胞因子表达。为了研究对 T 细胞激活的影响，我们用卵清蛋白（OVA）脉冲的、血吸虫诱导的 B 细胞与 OVA 特异性转基因 T 细胞共培养，与对照条件相比，观察到 Th2 细胞因子表达和 T 细胞增殖减少。即使在抗 CD3/28 的最佳 T 细胞刺激下，这种抑制作用仍然存在。阻断抑制性细胞因子 IL-10 或 TGF-β 仅略微恢复了 Th2 细胞因子的诱导。这些数据表明，血吸虫诱导的肺 B 细胞在对 TLR 配体产生细胞因子和诱导 Th2 细胞因子反应方面的能力受损，而与抗原呈递功能无关。这些发现强调了即使由相同类型的寄生虫诱导，也存在具有不同刺激或抑制特性的不同 B 细胞亚群。
