title: Critical role of CD28 in protective immunity against Salmonella typhimurium.
abstract: Efficient T cell activation requires both TCR signals and costimulatory signals. CD28 is one of the molecules that provide costimulatory signals for T cells. We used mice deficient in CD28 expression (CD28-/- mice) to analyze the role of CD28 in the immune response against the intracellular bacterium Salmonella typhimurium, the causative agent of murine typhoid fever. CD28-/- mice were highly susceptible to infection with wild-type S. typhimurium and even failed to control infection with attenuated aroA- S. typhimurium. More detailed analysis revealed that CD28-/- animals did not mount a T-dependent Ab response and were highly impaired in the production of IFN-gamma. Thus, CD28 cosignaling is crucial for immunity against S. typhimurium. To our knowledge, this is the first report describing an essential role for CD28 in protective immunity against an intracellular microbial pathogen.
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany. mittruecker@mpiib-berlin.mpg.de
authors.forename: H W
authors.initials: HW
authors.lastname: Mittrücker
authors.forename: A
authors.initials: A
authors.lastname: Köhler
authors.forename: T W
authors.initials: TW
authors.lastname: Mak
authors.forename: S H
authors.initials: SH
authors.lastname: Kaufmann
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000918:Antibody Specificity; D018106:CD28 Antigens / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics; D027682:Cation Transport Proteins; D020022:Genetic Predisposition to Disease / Q000235:genetics; D007106:Immune Sera / Q000008:administration & dosage; D007113:Immunity, Innate / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D012481:Salmonella Infections, Animal / Q000235:genetics* / Q000276:immunology* / Q000517:prevention & control; D012486:Salmonella typhimurium / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D000907:Antibodies, Bacterial; D018106:CD28 Antigens; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D007106:Immune Sera; D007371:Interferon-gamma; D008565:Membrane Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1