Optimal protection against <i>Salmonella</i> infection requires noncirculating memory.

Abstract

While CD4 Th1 cells are required for resistance to intramacrophage infections, adoptive transfer of Th1 cells is insufficient to protect against <i>Salmonella</i> infection. Using an epitope-tagged vaccine strain of <i>Salmonella</i>, we found that effective protection correlated with expanded <i>Salmonella</i>-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 <i>Salmonella</i> infection and should be the focus of vaccine strategies.