Surface phenotype and functionality of WNV specific T cells differ with age and disease severity

Area of Science:

• Immunology
• Virology
• Neuroscience

Background:

• West Nile virus (WNV) infection can cause severe neuroinvasive disease, especially in older adults.
• T cells are crucial for limiting WNV infection, with strong human T cell responses observed.
• Previous research identified dominant WNV peptide epitopes (SVG9 and SLF9) targeted by T cells.

Purpose of the Study:

• To investigate the role of T cell immunity in WNV disease severity and neurological outcomes.
• To assess memory phenotype and polyfunctional CD8+ T cell responses to dominant WNV epitopes in infected patients.
• To determine if T cell responses differ based on patient age and disease severity.

Main Methods:

• Analysis of peripheral blood mononuclear cells (PBMC) from 40 WNV-seropositive patients with varying symptoms.
• Staining PBMC with HLA-I multimers loaded with SVG9 and SLF9 epitopes.
• Multicolor flow cytometry to analyze WNV-specific CD8+ T cell responses, including phenotype and function.

Main Results:

• WNV-specific CD8+ T cells were detected months post-infection, with similar numbers in older and younger individuals.
• These T cells were predominantly monofunctional, expressing limited cytokine profiles (CD107a, MIP-1β, TNFα, IL-2, or IFNγ).
• Patients with neuroinvasion showed increased terminally differentiated, memory phenotype T cells (CD45RA+ CD27- CCR7- CD57+).

Conclusions:

• Terminally differentiated CD8+ T cells with a cytolytic profile are associated with WNV neuroinvasion.
• Monofunctional T cells persist after WNV infection, irrespective of age.
• Specific CD8+ T cell phenotypes correlate with disease outcomes in WNV infection, providing insights into pathogenesis.