IL-28B/IFN-lambda 3 drives granzyme B loading and significantly increases CTL killing activity in macaques.

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• Type III/lambda interferons (IFNs) are recently discovered cytokines with incompletely understood functions.
• Previous research on IFN-lambda 3 (IL-28B) primarily used small animal models, limiting translational relevance.
• The role of IFN-lambda 3 in adaptive immunity within larger, more relevant animal models remains largely uncharacterized.

Purpose of the Study:

• To investigate the influence of IFN-lambda 3 on adaptive immune responses in rhesus macaques.
• To assess the impact of IFN-lambda 3 on antigen-specific CD8(+) T-cell function, particularly cytotoxicity.
• To explore the potential of IFN-lambda 3 as an immunoadjuvant.

Main Methods:

• DNA vaccination was employed in rhesus macaques to study IFN-lambda 3's effects.
• Analysis of peripheral and mesenteric lymph node (MLN) CD8(+) T cells.
• Assessment of cytotoxic responses using CD107a and granzyme B coexpression, and perforin release.

Main Results:

• IFN-lambda 3 administration significantly enhanced antigen-specific CD8(+) T-cell cytotoxicity.
• IFN-lambda 3-treated animals showed increased CD8(+) T-cell CD107a and granzyme B coexpression and perforin release.
• CD8(+) T cells from MLN of IFN-lambda 3-treated macaques exhibited heightened granzyme B loading and induced greater target cell death.

Conclusions:

• IFN-lambda 3 demonstrates potent immunomodulatory effects, specifically enhancing CD8(+) T-cell cytotoxic functions.
• These findings highlight IFN-lambda 3's significant role in adaptive immunity in a relevant primate model.
• IFN-lambda 3 warrants further investigation as a potential immunoadjuvant for enhancing vaccine efficacy.