CD4+ T cell immunity to Salmonella is transient in the circulation
Newton G. Peres, Nancy Wang, Paul G. Whitney, Sven Engel, Meghanashree M. Shreenivas, Ian Comerford, Dianna M. Hocking, Anna Belen Erazo, Irmgard Förster, Andreas Kupz, Thomas Gebhardt, Shaun R. McColl, Stephen J. McSorley, Sammy Bedoui, Richard A. Strugnell
Abstract
While Salmonella enterica is seen as an archetypal facultative intracellular bacterial pathogen where protection is mediated by CD4+ T cells, identifying circulating protective cells has proved very difficult, inhibiting steps to identify key antigen specificities. Exploiting a mouse model of vaccination, we show that the spleens of C57BL/6 mice vaccinated with live-attenuated Salmonella serovar Typhimurium (S. Typhimurium) strains carried a pool of IFN-γ+ CD4+ T cells that could adoptively transfer protection, but only transiently. Circulating Salmonella-reactive CD4+ T cells expressed the liver-homing chemokine receptor CXCR6, accumulated over time in the liver and assumed phenotypic characteristics associated with tissue-associated T cells. Liver memory CD4+ T cells showed TCR selection bias and their accumulation in the liver could be inhibited by blocking CXCL16. These data showed that the circulation of CD4+ T cells mediating immunity to Salmonella is limited to a brief window after which Salmonella-specific CD4+ T cells migrate to peripheral tissues. Our observations highlight the importance of triggering tissue-specific immunity against systemic infections.