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Proc Natl Acad Sci U S A. 2018 Oct 9;115(41):10416-10421. doi: 10.1073/pnas.1808339115. Epub 2018 Sep 25.

Optimal protection against Salmonella infection requires noncirculating memory.

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Center for Comparative Medicine, University of California, Davis, CA 95616.
Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA 95616.
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia.
Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030.
Center for Comparative Medicine, University of California, Davis, CA 95616;


While CD4 Th1 cells are required for resistance to intramacrophage infections, adoptive transfer of Th1 cells is insufficient to protect against Salmonella infection. Using an epitope-tagged vaccine strain of Salmonella, we found that effective protection correlated with expanded Salmonella-specific memory CD4 T cells in circulation and nonlymphoid tissues. However, naive mice that previously shared a blood supply with vaccinated partners lacked T cell memory with characteristics of tissue residence and did not acquire robust protective immunity. Using a YFP-IFN-γ reporter system, we identified Th1 cells in the liver of immunized mice that displayed markers of tissue residence, including P2X7, ARTC2, LFA-1, and CD101. Adoptive transfer of liver memory cells after ARTC2 blockade increased protection against highly virulent bacteria. Taken together, these data demonstrate that noncirculating memory Th1 cells are a vital component of immunity to Salmonella infection and should be the focus of vaccine strategies.


CD4 T cell; Salmonella infection; protective immunity; tissue-resident memory; vaccines

[Available on 2019-04-09]
[Indexed for MEDLINE]

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