CD8 T cell abundance and early antiviral functions

Soerens, Andrew; Soerens, Andrew

RATIONALE: This project is designed to test the hypothesis that an abundant population of antigen-specific CD8 T cells within the lung at the time of an influenza type A (IAV) infection can significantly reduce the magnitude of the infection within the first hours after exposure.

METHODS: Preliminary data had shown that mice vaccinated via a heterologous prime boost boost (HPBB) regimen show reduced weight loss following IAV challenge, supporting the general efficacy of vaccine-induced memory T cells . To test our hypothesis, we first developed a modified HPBB regimen that uses intranasal challenge and results in a larger population of memory CD8 T cells in the lung. Mice with abundant memory CD8 T cells in the lungs as well as naive mice with no relevant preexisting memory were then challenged with a single-cycle, fluorescently labeled IAV expressing the peptide recognized by the vaccine-induced memory T cells. Twenty-four hours after infection with the single-cycle, mCherry expressing IAV, the mice were sacrificed and their lungs were frozen for quantitative imaging analysis to determine how many primary infected cells remained as measured by histological analysis of mCherry expressing cells.

RESULTS: While analysis is still ongoing, at present, vaccinated mice show an approximately eighteen-fold reduction in the number of primary-flu infected cells compared to previously naive mice.

CONCLUSIONS: These results show the value of abundant memory CD8 T cells in barrier tissues and demonstrate their ability to reduce viral burden in the initial hours after infection through the elimination of primary infected cells.