CD4+ T cell immunity to Salmonella is transient in the circulation

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.