Resolution of infection with attenuated Salmonella is an active process that requires CD4+ T cells. Here, we demonstrate that costimulation via the surface molecule CD28, but not antibody production by B cells, is required for clearance of attenuated aroA Salmonella enterica serovar typhimurium. In contrast, specific antibody is critical for vaccine-induced protection against virulent bacteria. Therefore, CD28+ CD4+ T cells are sufficient for clearance of avirulent Salmonella in naive hosts, whereas CD4+ T cells and specific antibodies are required for protection from virulent Salmonella in immune hosts.
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