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Culling of Activated CD4 T Cells during Typhoid Is Driven by Salmonella Virulence Genes¹

Center for Infectious Diseases and Microbiology Translational Research, Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, McGuire Translational Research Facility, University of Minnesota Medical School, Minneapolis, MN 55455

Pathogen-specific CD4 T cells are activated within a few hours of oral Salmonella infection and are essential for protective immunity. However, CD4 T cells do not participate in bacterial clearance until several weeks after infection, suggesting that Salmonella can inhibit or evade CD4 T cells that are activated at early time points. Here, we describe the progressive culling of initially activated CD4 T cells in Salmonella-infected mice. Loss of activated CD4 T cells was independent of early instructional programming, T cell precursor frequency, and Ag availability. In contrast, apoptosis of Ag-specific CD4 T cells was actively induced by live bacteria in a process that required Salmonella pathogenicity island-2 and correlated with increased expression of PD-L1. These data demonstrate efficient culling of initially activated Ag-specific CD4 cells by a microbial pathogen and document a novel strategy for bacterial immune evasion.

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 AI055743 and AI073672.

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

³ Abbreviations used in this paper: SPI, Salmonella pathogenicity island; HKST, heat-killed Salmonella serovar Typhimurium; PD-1, programmed cell death-1; PD-L1, ligands for PD-1.

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The JI 2009 182: 7329-7330. [Full Text]