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In vivo TCR signaling in CD4<sup>+</sup> T cells imprints a cell-intrinsic, transient low-motility pattern independent of chemokine receptor expression levels, or microtubular network, integrin, and protein kinase C activity

In vivo TCR signaling in CD4+ T cells imprints a cell-intrinsic, transient low-motility pattern independent of chemokine receptor expression levels, or microtubular network, integrin, and protein kinase C activity

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ACKERKNECHT, Markus, Mark A. HAUSER, Daniel F. LEGLER, Jens V. STEIN, 2015. In vivo TCR signaling in CD4+ T cells imprints a cell-intrinsic, transient low-motility pattern independent of chemokine receptor expression levels, or microtubular network, integrin, and protein kinase C activity. In: Frontiers in Immunology. 6, 297. eISSN 1664-3224

@article{Ackerknecht2015signa-32533, title={In vivo TCR signaling in CD4+ T cells imprints a cell-intrinsic, transient low-motility pattern independent of chemokine receptor expression levels, or microtubular network, integrin, and protein kinase C activity}, year={2015}, doi={10.3389/fimmu.2015.00297}, volume={6}, journal={Frontiers in Immunology}, author={Ackerknecht, Markus and Hauser, Mark A. and Legler, Daniel F. and Stein, Jens V.}, note={Article Number: 297} }

Stein, Jens V. Ackerknecht, Markus Hauser, Mark A. In vivo TCR signaling in CD4<sup>+</sup> T cells imprints a cell-intrinsic, transient low-motility pattern independent of chemokine receptor expression levels, or microtubular network, integrin, and protein kinase C activity Stein, Jens V. Hauser, Mark A. Legler, Daniel F. Legler, Daniel F. Ackerknecht, Markus 2016-01-12T12:57:50Z 2015 eng 2016-01-12T12:57:50Z Intravital imaging has revealed that T cells change their migratory behavior during physiological activation inside lymphoid tissue. Yet, it remains less well investigated how the intrinsic migratory capacity of activated T cells is regulated by chemokine receptor levels or other regulatory elements. Here, we used an adjuvant-driven inflammation model to examine how motility patterns corresponded with CCR7, CXCR4, and CXCR5 expression levels on ovalbumin-specific DO11.10 CD4<sup>+</sup> T cells in draining lymph nodes. We found that while CCR7 and CXCR4 surface levels remained essentially unaltered during the first 48–72 h after activation of CD4<sup>+</sup> T cells, their in vitro chemokinetic and directed migratory capacity to the respective ligands, CCL19, CCL21, and CXCL12, was substantially reduced during this time window. Activated T cells recovered from this temporary decrease in motility on day 6 post immunization, coinciding with increased migration to the CXCR5 ligand CXCL13. The transiently impaired CD4<sup>+</sup> T cell motility pattern correlated with increased LFA-1 expression and augmented phosphorylation of the microtubule regulator Stathmin on day 3 post immunization, yet neither microtubule destabilization nor integrin blocking could reverse TCR-imprinted unresponsiveness. Furthermore, protein kinase C (PKC) inhibition did not restore chemotactic activity, ruling out PKC-mediated receptor desensitization as mechanism for reduced migration in activated T cells. Thus, we identify a cell-intrinsic, chemokine receptor level-uncoupled decrease in motility in CD4<sup>+</sup> T cells shortly after activation, coinciding with clonal expansion. The transiently reduced ability to react to chemokinetic and chemotactic stimuli may contribute to the sequestering of activated CD4<sup>+</sup> T cells in reactive peripheral lymph nodes, allowing for integration of costimulatory signals required for full activation.

Dateiabrufe seit 12.01.2016 (Informationen über die Zugriffsstatistik)

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