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CCL19 and CCL21 induce a potent proinflammatory differentiation program in licensed dendritic cells
Author(s): Marsland BJ, Battig P, Bauer M, Ruedl C, Lassing U, Beerli RR, Dietmeier K, Ivanova L, Pfister T, Vogt L, Nakano H, Nembrini C, Saudan P, Kopf M, Bachmann MF
Source: IMMUNITY    Volume: 22    Issue: 4    Pages: 493-505    Published: APR 2005  
Times Cited: 69     References: 61     
Abstract: 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.
Document Type: Article
Language: English
Reprint Address: Bachmann, MF (reprint author), Cytos Biotechnol AG, Wagistr 25, CH-8952 Zurich, Switzerland
Addresses:
1. Cytos Biotechnol AG, CH-8952 Zurich, Switzerland
2. Swiss Fed Inst Technol, Dept Environm Sci, CH-8092 Zurich, Switzerland
3. Duke Univ, Ctr Med, Dept Med, Durham, NC 27710 USA
Publisher: CELL PRESS, 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA
Subject Category: Immunology
IDS Number: 923KU
ISSN: 1074-7613
DOI: 10.1016/j.immuni.2005.02.010
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