Adhesion shapes T cells for prompt and sustained T-cell receptor signalling.
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.
Contento
Rita Lucia
RL
Department of Translational Medicine, Istituto Clinico Humanitas IRCCS, Rozzano, Milan, Italy. Rita_Lucia.Contento@humanitasresearch.it
Campello
Silvia
S
Trovato
Anna Elisa
AE
Magrini
Elena
E
Anselmi
Fabio
F
Viola
Antonella
A
D000938:Antigen-Presenting Cells / Q000276:immunology; D015220:Calcium Channels / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology; D016764:Cell Polarity; D002478:Cells, Cultured; D018925:Chemokines / Q000276:immunology; D006801:Humans; D054992:Immunological Synapses / Q000276:immunology*; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008928:Mitochondria / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D015220:Calcium Channels; D015815:Cell Adhesion Molecules; D018925:Chemokines; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell