Faculté des sciences

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

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

In: The Journal of Immunology, 2013, vol. 190, no. 10, p. 5313–5320

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... Plus

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    Summary
    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.