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

  • Heidegger, Simon Center for Integrated Protein Science Munich, Klinische Pharmakologie, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Germany
  • Kirchner, Sophie-Kathrin Center for Integrated Protein Science Munich, Klinische Pharmakologie, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Germany
  • Stephan, Nicolas Center for Integrated Protein Science Munich, Klinische Pharmakologie, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Germany
  • Bohn, Bernadette Center for Integrated Protein Science Munich, Klinische Pharmakologie, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Germany
  • Suhartha, Nina Center for Integrated Protein Science Munich, Klinische Pharmakologie, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Germany
  • Hotz, Christian Center for Integrated Protein Science Munich, Klinische Pharmakologie, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Germany - Chair of Pharmacology, Department of Internal Medicine, University of Fribourg, Switzerland
  • Anz, David Center for Integrated Protein Science Munich, Klinische Pharmakologie, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Germany
  • Sandholzer, Nadja Center for Integrated Protein Science Munich, Klinische Pharmakologie, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Germany
  • Stecher, Bärbel Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Ludwig-Maximilians-Universität München, Germany
  • Rüssmann, Holger Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Ludwig-Maximilians-Universität München, Germany - Helios Clinic Emil von Behring, Institute for Microbiology, Immunology and Laboratory Medicine, Berlin, Germany
  • Endres, Stefan Center for Integrated Protein Science Munich, Klinische Pharmakologie, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Germany
  • Bourquin, Carole Center for Integrated Protein Science Munich, Klinische Pharmakologie, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Germany
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    15.05.2013
Published in:
  • The Journal of Immunology. - 2013, vol. 190, no. 10, p. 5313–5320
English 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.
Faculty
Faculté des sciences et de médecine
Department
Département de Médecine
Language
  • English
Classification
Biology
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/302988
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