During T-cell migration, cell polarity is orchestrated by chemokine receptors and adhesion molecules and involves the functional redistribution of molecules and organelles towards specific cell compartments. In contrast, it is generally believed that the cell polarity established when T cells meet antigen-presenting cells (APCs) is controlled by the triggered T-cell receptor (TCR). Here, we show that, during activation of human T lymphocytes by APCs, chemokines and LFA-1 establish cell polarity independently of TCR triggering. Chemokine-induced LFA-1 activation results in fast recruitment of MTOC and mitochondria towards the potential APC, a process required to amplify TCR Ca(2+) signalling at the upcoming immunological synapse, to promote nuclear translocation of transcriptional factor NFATc2 and boost CD25 expression. Our data show that the initial adhesive signals delivered by chemokines and LFA-1 shape and prepare T cells for antigen recognition.

Adhesion shapes T cells for prompt and sustained T-cell receptor signalling / R.L. Contento, S. Campello, A.E. Trovato, E. Magrini, F. Anselmi, A. Viola. - In: EMBO JOURNAL. - ISSN 0261-4189. - 29:23(2010 Dec 01), pp. 4035-4047. [10.1038/emboj.2010.258]

Adhesion shapes T cells for prompt and sustained T-cell receptor signalling

A. Viola
Ultimo
2010

Abstract

During T-cell migration, cell polarity is orchestrated by chemokine receptors and adhesion molecules and involves the functional redistribution of molecules and organelles towards specific cell compartments. In contrast, it is generally believed that the cell polarity established when T cells meet antigen-presenting cells (APCs) is controlled by the triggered T-cell receptor (TCR). Here, we show that, during activation of human T lymphocytes by APCs, chemokines and LFA-1 establish cell polarity independently of TCR triggering. Chemokine-induced LFA-1 activation results in fast recruitment of MTOC and mitochondria towards the potential APC, a process required to amplify TCR Ca(2+) signalling at the upcoming immunological synapse, to promote nuclear translocation of transcriptional factor NFATc2 and boost CD25 expression. Our data show that the initial adhesive signals delivered by chemokines and LFA-1 shape and prepare T cells for antigen recognition.
Chemokines ; Humans ; Jurkat Cells ; Mitochondria ; Lymphocyte Function-Associated Antigen-1 ; Immunological Synapses ; Cell Adhesion Molecules ; Lymphocyte Activation ; Calcium Channels ; Cell Polarity ; Cells, Cultured ; Receptors, Antigen, T-Cell ; Antigen-Presenting Cells ; Signal Transduction ; T-Lymphocytes
Settore MED/04 - Patologia Generale
1-dic-2010
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/165413
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