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TLR activation excludes circulating naive CD8+ T cells from gut-associated lymphoid organs in mice.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2013
Author Heidegger Simon, Kirchner Sophie-Kathrin, Stephan Nicolas, Bohn Bernadette, Suhartha Nina, Hotz Christian, Anz David, Sandholzer Nadja, Stecher Bärbel, Rüssmann Holger, Endres Stefan, Bourquin Carole,
Project Immunotherapy of gastric cancer: Enhancing T cell recruitment into tumors
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Original article (peer-reviewed)

Journal Journal of immunology (Baltimore, Md. : 1950)
Volume (Issue) 190(10)
Page(s) 5313 - 20
Title of proceedings Journal of immunology (Baltimore, Md. : 1950)
DOI 10.4049/jimmunol.1202280

Abstract

The trafficking of effector T cells is tightly regulated by the expression of site-specific sets of homing molecules. In contrast, naive T cells are generally assumed to express a uniform pattern of homing molecules and to follow a random distribution within the blood and secondary lymphoid organs. In this study, we demonstrate that systemic infection fundamentally modifies the trafficking of circulating naive CD8(+) T cells. We show that on naive CD8(+) T cells, the constitutive expression of the integrin α4β7 that effects their entry into GALT is downregulated following infection of mice with Salmonella typhimurium. We further show that this downregulation is dependent on TLR signaling, and that the TLR-activated naive CD8(+) T cells are blocked from entering GALT. This contrasts strongly with Ag-experienced effector T cells, for which TLR costimulation in the GALT potently upregulates α4β7 and enhances trafficking to intestinal tissues. Thus, TLR activation leads to opposite effects on migration of naive and effector CD8(+) T cells. Our data identify a mechanism that excludes noncognate CD8(+) T cells from selected immune compartments during TLR-induced systemic inflammation.
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