Critical role of CD28 in protective immunity against Salmonella typhimurium

Efficient T cell activation requires both TCR signals and costimulatory sig nals. CD28 is one of the molecules that provide costimulatory signals for T cells. We used mice deficient in CD28 expression (CD28(-/-) mice) to analy ze the role of CD28 in the immune response against the intracellular bacter ium Salmonella typhimurium, the causative agent of murine typhoid fever. CD 28(-/-) mice were highly susceptible to infection with wild-type S. typhimu rium and even failed to control infection with attenuated aroA(-) S. typhim urium. More detailed analysis revealed that CD28(-/-) animals did not mount a T-dependent Ab response and were highly impaired in the production of IF N-gamma, Thus, CD28 cosignaling is crucial for immunity against S. typhimur ium. To our knowledge, this is the first report describing an essential rol e for CD28 in protective immunity against an intracellular microbial pathog en.