Effector memory CD8 T cell response elicits Hepatitis E Virus genotype 3 pathogenesis in the elderly

Area of Science:

• Immunology
• Virology
• Gerontology

Background:

• Genotype 3 Hepatitis E virus (HEV-3) poses a significant threat to the aging population.
• A notable discrepancy exists in disease severity among older HEV-3 infected individuals, with over a third experiencing severe liver damage.

Purpose of the Study:

• To investigate the role of CD8 T cells in determining the clinical outcome of HEV-3 infection in immunocompetent elderly individuals.
• To identify immune correlates associated with symptomatic versus asymptomatic HEV-3 infection in the elderly.

Main Methods:

• Analysis of CD8 T cell populations (effector memory CD8 T cells) in HEV-3 infected elderly patients and healthy donors.
• Assessment of T cell activation markers, cytokine production, gene expression (T-Bet, granzyme B, CXCR3), and chemokine levels (CXCL9-10).
• Correlation of immune responses with clinical symptoms, viral load, and disease resolution.

Main Results:

• Symptomatic HEV-3 infection in the elderly is characterized by an expansion of highly activated effector memory CD8 T (EM) cells.
• These activated EM cells exhibit features of early T cell exhaustion, altered cytokine profiles, and increased expression of NKG2D, T-Bet, granzyme B, and CXCR3.
• Increased levels of inflammatory chemokines CXCL9-10 promote the recruitment of cytotoxic EM cells to the liver in symptomatic patients.

Conclusions:

• The study identifies CD8 T cell activation and exhaustion as critical immune correlates contributing to HEV-3 pathogenesis in the elderly.
• An overactive EM cell response is linked to severe liver disease, while a moderate response is associated with asymptomatic infection.
• These findings highlight the central role of EM cells in governing the outcome of HEV-3 infection and suggest potential therapeutic targets.