Toronto Centre for Liver Disease, Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.
Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis, Missouri, USA.
J Infect Dis. 2020 Jun 16;222(1):148-157. doi: 10.1093/infdis/jiaa064.
Interferon-α (IFN-α) can suppress production of T-cell polarizing cytokines or induce inhibitory antigen-presenting cells that suppress T-cell activation. Previous studies showed that IFN-α therapy fails to boost virus-specific T-cell immunity in patients with chronic hepatitis B virus infection. Our aim was to determine whether IFN-α exposure alters human antigen-presenting cell function in vivo.
We investigated the immunomodulatory effects using peripheral blood mononuclear cells from healthy donors exposed to IFN-α and chronic hepatitis B (CHB) patients starting IFN-α therapy.
IFN-α increased HLA-DR, CD80, CD86, and PD-L1 expression on healthy donor monocytes. In contrast to the activated phenotype, IFN-α inhibited Toll-like receptor-induced cytokine production and monocyte-induced T-cell proliferation. In CHB patients, peg-IFN treatment induced an interferon-stimulated gene signature in monocytes and increased HLA-DR, CD80, CD86, and PD-L1 expression. As early as 3 days after CHB patients started treatment, IFN-α inhibited monocyte cytokine production and T-cell stimulation ex vivo. IFN-α-mediated inhibition of IL-12 production, rather than inhibitory receptor expression, was responsible for inhibition of T-cell proliferation. Addition of IL-12 restored T-cell proliferation to baseline levels.
Understanding how professional antigen-presenting cells respond to immunomodulation is important for both new innate and adaptive-targeted immunotherapies.
NCT00962871.
干扰素-α（IFN-α）可以抑制 T 细胞极化细胞因子的产生，或诱导抑制性抗原呈递细胞，从而抑制 T 细胞的激活。先前的研究表明，IFN-α 治疗未能增强慢性乙型肝炎病毒感染患者的病毒特异性 T 细胞免疫。我们的目的是确定 IFN-α 暴露是否会改变人类抗原呈递细胞在体内的功能。
我们使用来自健康供体和开始 IFN-α 治疗的慢性乙型肝炎（CHB）患者的外周血单核细胞，研究了免疫调节作用。
IFN-α增加了健康供体单核细胞上 HLA-DR、CD80、CD86 和 PD-L1 的表达。与激活表型相反，IFN-α抑制了 Toll 样受体诱导的细胞因子产生和单核细胞诱导的 T 细胞增殖。在 CHB 患者中，聚乙二醇干扰素治疗诱导了单核细胞中的干扰素刺激基因特征，并增加了 HLA-DR、CD80、CD86 和 PD-L1 的表达。早在 CHB 患者开始治疗的 3 天后，IFN-α就抑制了单核细胞细胞因子的产生和体外 T 细胞的刺激。IFN-α 介导的抑制 IL-12 产生，而不是抑制性受体表达，是抑制 T 细胞增殖的原因。添加 IL-12 可将 T 细胞增殖恢复到基线水平。
了解专业抗原呈递细胞如何对免疫调节做出反应对于新的先天和适应性靶向免疫疗法都很重要。
NCT00962871。
