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1: J Immunol. 2007 May 15;178(10):6342-9.
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Innate immune activation of CD4 T cells in salmonella-infected mice is dependent on IL-18.

Srinivasan A, Salazar-Gonzalez RM, Jarcho M, Sandau MM, Lefrancois L, McSorley SJ.

Department of Medicine, and Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota Medical School, McGuire Translational Research Facility, Minneapolis, MN 55455, USA.

Production of IFN-gamma by CD4 T cells is generally thought to be mediated by TCR triggering, however, Ag-nonspecific activation of effector CD8 T cells has been reported in infection models. In this study, we demonstrate that Ag-experienced CD4 T cells in the spleen of Salmonella-infected mice acquire the capacity to rapidly secrete IFN-gamma in response to stimulation with bacterial lysate or LPS. This innate responsiveness of T cells was transient and most apparent during, and immediately following, active Salmonella infection. Furthermore, innate T cell production of IFN-gamma in response to bacterial lysate or LPS was Ag independent and could be induced in Listeria-infected mice and in the absence of MHC class II expression. IL-18 was required for maximal innate responsiveness of CD4 T cells in Salmonella-infected mice and for optimal bacterial clearance in vivo. These data demonstrate that CD4 T cells acquire the capacity to respond to innate stimuli during active bacterial infection, a process that may contribute significantly to amplifying effector responses in vivo.

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PMID: 17475863 [PubMed - indexed for MEDLINE]