WhileSalmonella entericais 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-attenuatedSalmonellaserovar Typhimurium (S. Typhimurium) strains carried a pool of IFN-γ⁺CD4⁺T cells that could adoptively transfer protection, but only transiently. CirculatingSalmonella-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 toSalmonellais limited to a brief window after whichSalmonella-specific CD4⁺T cells migrate to peripheral tissues. Our observations highlight the importance of triggering tissue-specific immunity against systemic infections.