PT  - JOURNAL ARTICLE
AU  - Mairene Coto-Llerena
AU  - Marco Lepore
AU  - Julian Spagnuolo
AU  - Daniela Di Blasi
AU  - Diego Calabrese
AU  - Aleksei Suslov
AU  - Glenn Bantug
AU  - Francois HT Duong
AU  - Luigi M Terracciano
AU  - Gennaro De Libero
AU  - Markus H Heim
TI  - Interferon lambda 4 can directly activate human CD19<sup>+</sup> B cells and CD8<sup>+</sup> T cells
AID  - 10.26508/lsa.201900612
DP  - 2021 Jan 01
TA  - Life Science Alliance
PG  - e201900612
VI  - 4
IP  - 1
4099  - https://www.life-science-alliance.org/content/4/1/e201900612.short
4100  - https://www.life-science-alliance.org/content/4/1/e201900612.full
SO  - Life Sci. Alliance2021 Jan 01; 4
AB  - 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.