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Interferon lambda 4 can directly activate human CD19+ B cells and CD8+ T cells.
Life Science Alliance ( IF 4.4 ) Pub Date : 2020-11-06 , DOI: 10.26508/lsa.201900612
Mairene Coto-Llerena 1 , Marco Lepore 2 , Julian Spagnuolo 2 , Daniela Di Blasi 1, 2 , Diego Calabrese 1 , Aleksei Suslov 1 , Glenn Bantug 3 , Francois Ht Duong 1 , Luigi M Terracciano 4 , Gennaro De Libero 5 , Markus H Heim 6, 7
Affiliation  

Compared with the ubiquitous expression of type I (IFNα and IFNβ) interferon receptors, type III (IFNλ) interferon receptors are mainly expressed in epithelial cells of mucosal barriers of the of the intestine and respiratory tract. Consequently, IFNλs are important for innate pathogen defense in the lung and intestine. IFNλs also determine the outcome of hepatitis C virus (HCV) infections, with IFNλ4 inhibiting spontaneous clearance of HCV. Because viral clearance is dependent on T cells, we explored if IFNλs can directly bind to and regulate human T cells. We found that human B cells and CD8+ T cells express the IFNλ receptor and respond to IFNλs, including IFNλ4. IFNλs were not inhibitors but weak stimulators of B- and T-cell responses. Furthermore, IFNλ4 showed neither synergistic nor antagonistic effects in co-stimulatory experiments with IFNλ1 or IFNα. Multidimensional flow cytometry of cells from liver biopsies of hepatitis patients from IFNλ4-producers showed accumulation of activated CD8+ T cells with a central memory-like phenotype. In contrast, CD8+ T cells with a senescent/exhausted phenotype were more abundant in IFNλ4-non-producers. It remains to be elucidated how IFNλ4 promotes CD8 T-cell responses and inhibits the host immunity to HCV infections.

中文翻译:

干扰素 lambda 4 可以直接激活人 CD19+ B 细胞和 CD8+ T 细胞。

与I型(IFNα和IFNβ)干扰素受体的普遍表达相比,III型(IFNλ)干扰素受体主要在肠道和呼吸道粘膜屏障的上皮细胞中表达。因此,IFNλs对于肺和肠中的先天病原体防御很重要。IFNλs 还决定丙型肝炎病毒 (HCV) 感染的结果,IFNλ4 抑制 HCV 的自发清除。由于病毒清除依赖于 T 细胞,我们探索了 IFNλs 是否可以直接结合并调节人类 T 细胞。我们发现人类 B 细胞和 CD8 +T 细胞表达 IFNλ 受体并响应 IFNλs,包括 IFNλ4。IFNλs 不是抑制剂,而是 B 和 T 细胞反应的弱刺激剂。此外,在与 IFNλ1 或 IFNα 的共刺激实验中,IFNλ4 既没有显示出协同作用也没有显示出拮抗作用。来自 IFNλ4 生产者的肝炎患者肝脏活检细胞的多维流式细胞术显示具有中枢记忆样表型的活化 CD8 + T 细胞的积累。相比之下,具有衰老/耗竭表型的CD8 + T 细胞在 IFNλ4 非生产者中更为丰富。IFNλ4 如何促进 CD8 T 细胞反应并抑制宿主对 HCV 感染的免疫力仍有待阐明。
更新日期:2020-11-13
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