Surface-bound chemokines capture and prime T cells for synapse formation.
T cell activation in vivo occurs in a lymphoid milieu that presents chemotactic and T cell receptor signals concurrently. Here we demonstrate that T cell zone chemokines such as CCL21 are bound to the surface of lymph node dendritic cells. Contact with antigen-presenting cells bearing chemokines costimulated T cells by a previously unknown two-step contact mechanism. T cells initially formed an antigen-independent 'tethered' adhesion on chemokine-bearing antigen-presenting cells. The formation of those tethers superseded T cell receptor signaling and immunological synapse formation. However, chemokine-tethered T cells were hyper-responsive to subsequent contacts with antigen-presenting cells. Thus, T cells are costimulated 'in trans' and sequentially after initial engagement with their chemokine-rich environment.
Friedman
Rachel S
RS
The Department of Pathology, University of California at San Francisco, San Francisco, California 94143, USA.
Jacobelli
Jordan
J
Krummel
Matthew F
MF
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D054421:Chemokine CCL21; D018925:Chemokines / Q000276:immunology* / Q000494:pharmacology; D019742:Chemokines, CC / Q000032:analysis / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008024:Ligands; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D015703:Antigens, CD; C515479:Ccl21c protein, mouse; C515371:Ccr7 protein, mouse; D015815:Cell Adhesion Molecules; D054421:Chemokine CCL21; D018925:Chemokines; D019742:Chemokines, CC; C480027:ICAM-2 protein, mouse; C090509:Icam1 protein, mouse; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D018799:Intercellular Adhesion Molecule-1