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

J Immunol. 2010 Aug 15;185(4):2442-9. doi: 10.4049/jimmunol.1000743. Epub 2010 Jul 16.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • B7-1 Antigen / genetics
  • B7-1 Antigen / immunology*
  • B7-H1 Antigen
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / immunology
  • Cell Proliferation
  • Clone Cells / immunology
  • Clone Cells / metabolism
  • Flow Cytometry
  • Immunity / immunology*
  • Lymphocyte Count
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Peptides / deficiency
  • Peptides / genetics
  • Peptides / immunology*
  • Salmonella / immunology
  • Salmonella Infections / genetics
  • Salmonella Infections / immunology*
  • Salmonella Infections / mortality
  • Survival Rate
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Time Factors

Substances

  • B7-1 Antigen
  • B7-H1 Antigen
  • Cd274 protein, mouse
  • Membrane Glycoproteins
  • Peptides