CCL19 and CCL21 induce a potent proinflammatory differentiation program in licensed dendritic cells.
Dendritic cells (DCs) are key instigators of adaptive immune responses. Using an alphaviral expression cloning technology, we have identified the chemokine CCL19 as a potent inducer of T cell proliferation in a DC-T cell coculture system. Subsequent studies showed that CCL19 enhanced T cell proliferation by inducing maturation of DCs, resulting in upregulation of costimulatory molecules and the production of proinflammatory cytokines. Moreover, CCL19 programmed DCs for the induction of T helper type (Th) 1 rather than Th2 responses. Importantly, only activated DCs that migrated from the periphery to draining lymph nodes, but not resting steady-state DCs residing within lymph nodes, expressed high levels of CCR7 in vivo and responded to CCL19 with the production of proinflammatory cytokines. Migrating DCs isolated from mice genetically deficient in CCL19 and CCL21 (plt/plt) presented an only partially mature phenotype, highlighting the importance of these chemokines for full DC maturation in vivo. Our findings indicate that CCL19 and CCL21 are potent natural adjuvants for terminal activation of DCs and suggest that chemokines not only orchestrate DC migration but also regulate their immunogenic potential for the induction of T cell responses.
Marsland
Benjamin J
BJ
Molecular Biomedicine, Department of Environmental Sciences, Swiss Federal Institute of Technology, CH-8092 Zurich, Switzerland.
Bättig
Patrick
P
Bauer
Monika
M
Ruedl
Christiane
C
Lässing
Ute
U
Beerli
Roger R
RR
Dietmeier
Klaus
K
Ivanova
Lidia
L
Pfister
Thomas
T
Vogt
Lorenz
L
Nakano
Hideki
H
Nembrini
Chiara
C
Saudan
Philippe
P
Kopf
Manfred
M
Bachmann
Martin F
MF
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D011956:Receptors, Cell Surface / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D051193:Toll-Like Receptors; D015854:Up-Regulation
C515461:Ccl19 protein, mouse; C515479:Ccl21c protein, mouse; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC; D016207:Cytokines; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors