Multiple antigen encounters decrease memory CD8 T cell-mediated protection against chronic viral infection (132.8)

Abstract

Abstract While multiple studies demonstrate the enhanced protective capacity of primary memory compared to naive CD8 T cells, much less is known about the function and properties of memory CD8 T cells that have received multiple antigen exposures through either recurring infections or from booster immunizations. Therefore, we analyzed the ability of primary and secondary memory CD8 T cells to protect against a variety of pathogens expressing a common antigen. Our findings demonstrate that secondary memory CD8 T cells provide better per cell protective capacity than primary memory CD8 T cells against acute infections with both LCMV Armstrong and Listeria monocytogenes. In contrast, while primary memory CD8 T cells were able to effectively prevent a chronic infection with LCMV clone 13, an equal number of secondary memory T cells were unable to clear virus and became functionally exhausted. Delayed re-expression of CD62L on the secondary memory CD8 T cell population affected control of LCMV clone 13, as sorted CD62Lhi primary and secondary memory CD8 T cells were equally capable in preventing chronic infection. Overall, these studies demonstrate that multiple antigen encounters impact the ability of memory CD8 T cells to protect against different pathogens, information that should be considered during vaccine design. Supported by NIH (RO1-AI42767 to JTH and T32-AI07343 to JCN)