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

Peres, Newton G.;Wang, Nancy;Whitney, Paul;Engel, Sven;Shreenivas, Meghanashree M.;Comerford, Ian;Hocking, Dianna M.;Erazo, Anna B.;Forster, Irmgard;Kupz, Andreas;Gebhardt, Thomas;McColl, Shaun R.;McSorley, Stephen J.;Bedoui, Sammy;Strugnell, Richard A.

Andreas Kupz

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.

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PLoS Pathogens

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1553-7374

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Public Library of Science

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DOI

10.1371/journal.ppat.1010004