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

• DOI: 10.1371/journal.ppat.1010004
• Publication Date: 2021-10-25T17:31:46Z
• Authors: Newton G. Peres; Nancy Wang; Paul Whitney; Sven Engel; Meghanashree M. S...; Ian Comerford; Dianna M. Hocking; Anna B. Erazo; Irmgard Förster; Andreas Kupz; Thomas Gebhardt; Shaun R. McColl; Stephen J. McSorley; Sammy Bedoui; Richard A. Strugnell
• Keywords: CD4-Positive T-Lymphocytes; Male; Salmonella typhimurium; 570; QH301-705.5; Clinical Sciences; Immunology; 610; Inbred C57BL; Microbiology; Vaccine Related; Mice; 03 medical and health sciences; Biodefense; Virology; 2.1 Biological and endogenous factors; Animals; Biology (General); Salmonella Infections, Animal; 0303 health sciences; Biomedical and Clinical Sciences; Animal; Liver Disease; Inflammatory and immune system; Medical microbiology; RC581-607; Foodborne Illness; 3. Good health; Mice, Inbred C57BL; Infectious Diseases; Emerging Infectious Diseases; Liver; Medical Microbiology; Salmonella Infections; Immunization; Female; Immunologic diseases. Allergy; Digestive Diseases; Infection; Immunologic Memory; Research Article

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.