Polyclonal but not monoclonal circulating memory CD4T cells attenuate the severity ofbacteremia.

Abstract

bacteremia causes significant morbidity and mortality. Treatment of staphylococcal infections is hindered by widespread antibiotic resistance, and attempts to develop anvaccine have failed. Improvedtreatment and infection prevention options require a deeper understanding of the correlates of protective immunity. CD4T cells have been identified as key orchestrators in the defense against, but uncertainties persist regarding the subset, polarity, and breadth of the memory CD4T-cell pool required for protection. Here, using a mouse model of systemicinfection, we discovered that the breadth of bacterium-specific memory CD4T-cell pool is a critical factor for protective immunity against invasiveinfections. Seeding mice with a monoclonal bacterium-specific circulating memory CD4T-cell population failed to protect against systemicinfection; however, the introduction of a polyclonal and polyfunctional memory CD4T-cell pool significantly reduced the bacterial burden. Our findings support the development of a multi-epitope T-cell-basedvaccine, as a strategy to mitigate the severity ofbacteremia.