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Innate Immune Activation of CD4 T Cells in Salmonella-Infected Mice Is Dependent on IL-18¹

Aparna Srinivasan^*, Rosa-Maria Salazar-Gonzalez^*, Michael Jarcho^*, Michelle M. Sandau, Leo Lefrancois and Stephen J. McSorley^2,*

^* Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, and Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota Medical School, McGuire Translational Research Facility, Minneapolis, MN 55455; Center for Immunology and Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN 55455; and Division of Immunology, Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030

Production of IFN- 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- 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- 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants AI056172 (to L.L. and S.J.M.) and AI055743 (to S.J.M.).

² Address correspondence and reprint requests to Dr. Stephen J. McSorley, Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, and Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota Medical School, McGuire Translational Research Facility, TRF DC 2873, 2001 6th Street SE, Minneapolis, MN 55455. E-mail address: mcsor002{at}umn.edu

³ Abbreviations used in this paper: Wt, wild type; LCMV, lymphocytic choriomeningitis virus; MHC II, MHC class II; HKST, heat-killed S. typhimurium; HKLM, heat-killed Listeria.

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