Interferon lambda 4 can directly activate human CD19+ B cells and CD8+ T cells.

ABSTRACT: Compared with the ubiquitous expression of type I (IFN? and IFN?) interferon receptors, type III (IFN?) interferon receptors are mainly expressed in epithelial cells of mucosal barriers of the of the intestine and respiratory tract. Consequently, IFN?s are important for innate pathogen defense in the lung and intestine. IFN?s also determine the outcome of hepatitis C virus (HCV) infections, with IFN?4 inhibiting spontaneous clearance of HCV. Because viral clearance is dependent on T cells, we explored if IFN?s can directly bind to and regulate human T cells. We found that human B cells and CD8+ T cells express the IFN? receptor and respond to IFN?s, including IFN?4. IFN?s were not inhibitors but weak stimulators of B- and T-cell responses. Furthermore, IFN?4 showed neither synergistic nor antagonistic effects in co-stimulatory experiments with IFN?1 or IFN?. Multidimensional flow cytometry of cells from liver biopsies of hepatitis patients from IFN?4-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 IFN?4-non-producers. It remains to be elucidated how IFN?4 promotes CD8 T-cell responses and inhibits the host immunity to HCV infections.

SUBMITTER: Coto-Llerena M 

PROVIDER: S-EPMC7668538 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature