CC Chemokine Ligand 19 Secreted by Mature Dendritic Cells Increases Naive T Cell Scanning Behavior and Their Response to Rare Cognate Antigen

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Abstract
For immune responses to take place, naive T cells have to encounter, adhere to, and be stimulated by dendritic cells (DCs). In murine lymph nodes, T cells move randomly and scan the surface of multiple DCs. The factors controlling this motility as well as its consequences remain unclear. We have monitored by video-imaging the earliest steps of the interaction between human DCs and autologous naive CD4+ T cells in the absence of exogenous Ags. Mature, but not immature, DCs were able to elicit small calcium responses in naive T cells along with cell polarization and random motility, resulting in an efficient scanning of DC surfaces by T cells. We identified CCL19 as a key factor enabling all these early T cell responses, including the occurrence of calcium transients. Because this chemokine did not influence the strength of naive T cell adhesion to DCs, enhanced LFA-1 affinity for ICAM-1 was not the main mechanism by which CCL19 increased Ag-independent calcium transients. However, concomitantly to T cell motility, CCL19 augmented the frequency of T cell responses to rare anti-CD3/CD28-coated beads, used as surrogate APCs. We thus propose a new role for CCL19 in humans: by conditioning T cells into a motile DC-scanning state, this chemokine promotes Ag-independent responses and increases the probability of cognate MHC-peptide encounter.