PMID- 15845453 OWN - NLM STAT- MEDLINE DCOM- 20050531 LR - 20071115 IS - 1074-7613 (Print) IS - 1074-7613 (Linking) VI - 22 IP - 4 DP - 2005 Apr TI - CCL19 and CCL21 induce a potent proinflammatory differentiation program in licensed dendritic cells. PG - 493-505 AB - 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. FAU - Marsland, Benjamin J AU - Marsland BJ AD - Molecular Biomedicine, Department of Environmental Sciences, Swiss Federal Institute of Technology, CH-8092 Zurich, Switzerland. FAU - Battig, Patrick AU - Battig P FAU - Bauer, Monika AU - Bauer M FAU - Ruedl, Christiane AU - Ruedl C FAU - Lassing, Ute AU - Lassing U FAU - Beerli, Roger R AU - Beerli RR FAU - Dietmeier, Klaus AU - Dietmeier K FAU - Ivanova, Lidia AU - Ivanova L FAU - Pfister, Thomas AU - Pfister T FAU - Vogt, Lorenz AU - Vogt L FAU - Nakano, Hideki AU - Nakano H FAU - Nembrini, Chiara AU - Nembrini C FAU - Saudan, Philippe AU - Saudan P FAU - Kopf, Manfred AU - Kopf M FAU - Bachmann, Martin F AU - Bachmann MF LA - eng PT - Journal Article PL - United States TA - Immunity JT - Immunity JID - 9432918 RN - 0 (Ccl19 protein, mouse) RN - 0 (Ccl21c protein, mouse) RN - 0 (Chemokine CCL19) RN - 0 (Chemokine CCL21) RN - 0 (Chemokines, CC) RN - 0 (Cytokines) RN - 0 (Membrane Glycoproteins) RN - 0 (Receptors, Cell Surface) RN - 0 (Toll-Like Receptors) SB - IM MH - Animals MH - Cell Differentiation/immunology MH - Chemokine CCL19 MH - Chemokine CCL21 MH - Chemokines, CC/genetics/isolation & purification/*physiology MH - Cytokines/biosynthesis MH - Dendritic Cells/*cytology/immunology/metabolism MH - Gene Expression MH - Membrane Glycoproteins/metabolism MH - Mice MH - Receptors, Cell Surface/metabolism MH - T-Lymphocytes/immunology MH - Th1 Cells/immunology MH - Toll-Like Receptors MH - Up-Regulation EDAT- 2005/04/23 09:00 MHDA- 2005/06/01 09:00 CRDT- 2005/04/23 09:00 PHST- 2004/11/08 00:00 [received] PHST- 2005/02/10 00:00 [revised] PHST- 2005/02/23 00:00 [accepted] PHST- 2005/04/23 09:00 [pubmed] PHST- 2005/06/01 09:00 [medline] PHST- 2005/04/23 09:00 [entrez] AID - S1074-7613(05)00097-X [pii] AID - 10.1016/j.immuni.2005.02.010 [doi] PST - ppublish SO - Immunity. 2005 Apr;22(4):493-505. doi: 10.1016/j.immuni.2005.02.010.