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

Area of Science:

• Immunology
• Virology

Background:

• Type I interferons (IFNα, IFNβ) have widespread receptor expression.
• Type III interferons (IFNλ) primarily target epithelial cells in mucosal barriers.
• IFNλs are crucial for innate immunity in the gut and respiratory tract.
• IFNλ4 is implicated in hindering spontaneous hepatitis C virus (HCV) clearance.

Purpose of the Study:

• To investigate the direct binding and regulatory effects of IFNλs on human T cells.
• To understand the role of IFNλs, particularly IFNλ4, in T cell responses and HCV infection.

Main Methods:

• Analysis of IFNλ receptor expression on human B cells and CD8+ T cells.
• Assessment of T and B cell responses to various IFNλ subtypes and IFNα.
• Multidimensional flow cytometry on liver biopsy samples from hepatitis patients.

Main Results:

• Human B cells and CD8+ T cells express the IFNλ receptor and respond to IFNλs, including IFNλ4.
• IFNλs act as weak stimulators, not inhibitors, of B and T cell responses.
• IFNλ4 demonstrated no synergistic or antagonistic effects with IFNλ1 or IFNα in co-stimulation.
• Analysis of liver biopsies revealed distinct CD8+ T cell phenotypes based on IFNλ4 production: activated memory cells in producers versus senescent/exhausted cells in non-producers.

Conclusions:

• IFNλs can directly interact with and modulate human T and B cells.
• IFNλ4 influences CD8+ T cell populations, potentially affecting HCV clearance.
• Further research is needed to clarify the mechanisms by which IFNλ4 impacts CD8+ T cell immunity and HCV infection.