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.
Lee
Seung-Joo
SJ
Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Center for Infectious Diseases and Microbiology Translational Research, McGuire Translational Research Facility, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
O'Donnell
Hope
H
McSorley
Stephen J
SJ
D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D060890:B7-H1 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D007109:Immunity / Q000276:immunology*; D018655:Lymphocyte Count; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010455:Peptides / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D012475:Salmonella / Q000276:immunology; D012480:Salmonella Infections / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D015996:Survival Rate; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D008562:Membrane Glycoproteins; D010455:Peptides