B7-H1 (Programmed Cell Death Ligand 1) Is Required for the Development of Multifunctional Th1 Cells and Immunity to Primary, but Not Secondary, Salmonella Infection

Robust Ab and CD4 T cell responses are required for the resolution of Salmonella infection in susceptible mice. In this study, we examined the role of B7-H1 (programmed cell death ligand 1) in resistance to primary Salmonella infection. Infected B7-H1-deficient mice had significantly higher bacterial burdens at day 21 and day 35 postinfection compared with wild-type mice, demonstrating that B7-H1 plays an important role in immunity to Salmonella. B7-H1-deficient and wild-type mice both generated Salmonella-specific IgM and IgG2c Ab responses to infection, and clonal expansion of endogenous and adoptively transferred Salmonella-specific CD4 T cells was similar in both groups. However, although Salmonella-specific IFN-gamma-producing Th1 CD4 T cells were generated in Salmonella-infected B7-H1-deficient mice, these cells did not expand to the level observed in wild-type mice. Furthermore, fewer multifunctional Th1 cells that simultaneously secreted IFN-gamma, TNF-alpha, and IL-2 were detected in Salmonella-infected B7-H1-deficient mice. Together, these data demonstrate that B7-H1 is required for the generation of multifunctional Th1 responses and optimal protective immunity to primary Salmonella infection. The Journal of Immunology, 2010, 185: 2442-2449.