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J Leukoc Biol. 2007 Feb;81(2):403-11. Epub 2006 Aug 17.

Pivotal advance: exposure to LPS suppresses CD4+ T cell cytokine production in Salmonella-infected mice and exacerbates murine typhoid.

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Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota Medical School, McGuire Translational Research Facility, Minneapolis, MN 55455, USA.


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-alpha. 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.

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