CC chemokine ligand 19 secreted by mature dendritic cells increases naive T cell scanning behavior and their response to rare cognate antigen.
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.
Kaiser
Andrew
A
Immuno-Designed Molecules, Paris, France.
Donnadieu
Emmanuel
E
Abastado
Jean-Pierre
JP
Trautmann
Alain
A
Nardin
Alessandra
A
D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002118:Calcium / Q000502:physiology; D002448:Cell Adhesion / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D016764:Cell Polarity / Q000276:immunology; D002478:Cells, Cultured; D054415:Chemokine CCL19; D019742:Chemokines, CC / Q000378:metabolism* / Q000502:physiology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D018715:Microscopy, Video; D016192:Resting Phase, Cell Cycle / Q000276:immunology*
C515460:CCL19 protein, human; D018106:CD28 Antigens; D017252:CD3 Complex; D054415:Chemokine CCL19; D019742:Chemokines, CC; D002118:Calcium