Recent Thymic Emigrants and Chronic Salmonellosis: How New T Cells Combat an Old Infection

Abstract Typhoid fever, caused by infection with Salmonella bacteria affects approximately 21 million people annually, killing nearly 200,000 and yet the immunological response to this infection is poorly understood. Recent thymic emigrants (RTEs) are the youngest subset of peripheral T cells, which are known to differ in how they functionally contribute to the naïve T cell pool. This distinctive cell population is known to contribute to the maintenance of T cell receptor diversity in the peripheral T cell pool, but their involvement in combating chronic bacterial infections, such as typhoid fever, has not been explored. In the present study, we hypothesized that RTEs are essential contributors to the CD4 T cell response during persistent Salmonella Typhimurium (ST) infection, which predominantly relies on helper T cell immunity to control bacteria. Here, we show that thymectomy of adult mice prior to oral infection with ST leads to increased mortality in addition to significantly increased bacterial burdens in the spleen, mesenteric lymph nodes and liver 30 days post-infection compared to sham surgical controls, suggesting Salmonella-specific RTEs may contribute to bacterial clearance. Surprisingly, thymectomized animals also demonstrated expanded numbers of peripheral Salmonella-specific T cells, compared to control animals, implying that these existing cells are somehow incapable of controlling infection in the absence of RTEs. The results of this study provide insight into how new pathogen-specific T cells leaving the thymus participate in combatting a persistent bacterial infection.