RT Journal Article
SR Electronic
T1 Interferon lambda 4 can directly activate human CD19<sup>+</sup> B cells and CD8<sup>+</sup> T cells
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201900612
DO 10.26508/lsa.201900612
VO 4
IS 1
A1 Mairene Coto-Llerena
A1 Marco Lepore
A1 Julian Spagnuolo
A1 Daniela Di Blasi
A1 Diego Calabrese
A1 Aleksei Suslov
A1 Glenn Bantug
A1 Francois HT Duong
A1 Luigi M Terracciano
A1 Gennaro De Libero
A1 Markus H Heim
YR 2021
UL https://www.life-science-alliance.org/content/4/1/e201900612.abstract
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.