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Exposure to LPS suppresses CD4+ T cell cytokine production in Salmonella‐infected mice and exacerbates murine typhoid

A number of studies have documented suppression of lymphocyte activation in mice infected with Salmonella. Here, we describe incomplete activation of CD4+ T cells following intravenous injection of specific peptide and LPS into Salmonella‐infected mice. Although antigen‐specific CD4+ T cells were activated by peptide/LPS to increase surface CD69 expression, they did not produce IL‐2 or TNF‐α. Suppression of cytokine production did not require prolonged exposure of the T cells to the Salmonella‐infected environment, was not antigen specific, but was dependent upon the presence of LPS during stimulation. These data suggest that Salmonella‐infected mice are exquisitely sensitive to the generation of a suppressive environment following innate immune stimulation with LPS. In agreement with this interpretation, repeated low‐dose administration of LPS caused uncontrolled replication of attenuated Salmonella in vivo.