title: TLR activation excludes circulating naive CD8+ T cells from gut-associated lymphoid organs in mice.
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.
authors.affiliation: Center for Integrated Protein Science Munich, Klinische Pharmakologie, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, 80336 Munich, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Heidegger
authors.forename: Sophie-Kathrin
authors.initials: SK
authors.lastname: Kirchner
authors.forename: Nicolas
authors.initials: N
authors.lastname: Stephan
authors.forename: Bernadette
authors.initials: B
authors.lastname: Bohn
authors.forename: Nina
authors.initials: N
authors.lastname: Suhartha
authors.forename: Christian
authors.initials: C
authors.lastname: Hotz
authors.forename: David
authors.initials: D
authors.lastname: Anz
authors.forename: Nadja
authors.initials: N
authors.lastname: Sandholzer
authors.forename: Bärbel
authors.initials: B
authors.lastname: Stecher
authors.forename: Holger
authors.initials: H
authors.lastname: Rüssmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Endres
authors.forename: Carole
authors.initials: C
authors.lastname: Bourquin
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology; D015536:Down-Regulation; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D016023:Integrins / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin; D012480:Salmonella Infections / Q000276:immunology; D012486:Salmonella typhimurium / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D051193:Toll-Like Receptors / Q000276:immunology* / Q000378:metabolism
chemical_list: D007093:Imidazoles; D016023:Integrins; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6; D051193:Toll-Like Receptors; C071777:integrin alpha4beta7; D010047:Ovalbumin; C402365:resiquimod