Dynamics of Tissue-Specific CD8⁺ T Cell Responses during West Nile Virus Infection

Area of Science:

• Immunology
• Virology
• Neuroscience

Background:

• West Nile virus (WNV) is a major cause of mosquito-borne encephalitis globally.
• CD8+ T cells play a vital role in controlling WNV infection and providing protection.
• Current therapeutic and vaccine options for human WNV infection are limited.

Purpose of the Study:

• To characterize a novel T cell receptor (TCR)-transgenic mouse model (WNV-I mice) specific for a WNV NS4B epitope.
• To investigate the kinetics, expansion, differentiation, and function of CD8+ T cells during WNV infection in this model.
• To explore the role of CD8+ T cells in controlling viral burden within the central nervous system (CNS).

Main Methods:

• Generation and characterization of TCR-transgenic WNV-I mice.
• Adoptive transfer of WNV-I CD8+ T cells into recipient mice.
• In vivo intravascular immune cell staining to analyze T cell populations.
• Analysis of T cell differentiation, polyfunctionality (IFN-γ, TNF-α), tissue residency (CD69+, CD103+), and viral clearance in the spleen and CNS.

Main Results:

• WNV-I CD8+ T cells exhibited expansion and contraction phases similar to endogenous responses.
• Red-pulp T cells were more effector-like, while white-pulp T cells showed greater memory precursor differentiation.
• CNS-infiltrating WNV-I CD8+ T cells were polyfunctional, tissue-resident, persisted through day 15 postinfection, and reduced viral load.
• These T cells demonstrated effector functions and reduced WNV burden in the brain.

Conclusions:

• The WNV-I TCR-transgenic mouse model is a valuable tool for studying CD8+ T cell-mediated immunity against WNV.
• Characterization of T cell subsets provides insights into mechanisms of viral control and protection in the CNS.
• Findings advance understanding of host-pathogen interactions in WNV encephalitis and inform future therapeutic strategies.