Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Regulation of Homeostatic Chemokine Expression and Cell Trafficking During Immune Responses
Scott N. Mueller,1*Karoline A. Hosiawa-Meagher,2Bogumila T. Konieczny,1Brandon M. Sullivan,3Martin F. Bachmann,4Richard M. Locksley,3Rafi Ahmed,1Mehrdad Matloubian2
The chemokines CCL21 and CXCL13 are immune factors that dictatehoming and motility of lymphocytes and dendritic cells in lymphoidtissues. However, the means by which these chemokines are regulatedand how they influence cell trafficking during immune responsesremain unclear. We show that CCL21 and CXCL13 are transientlydown-regulated within lymphoid tissues during immune responsesby a mechanism controlled by the cytokine interferon-. Thismodulation was found to alter the localization of lymphocytesand dendritic cells within responding lymphoid tissues. As aconsequence, priming of T cell responses to a second distinctpathogen after chemokine modulation became impaired. We proposethat this transient chemokine modulation may help orchestratelocal cellularity, thus minimizing competition for space andresources in activated lymphoid tissues.
1 Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA. 2 Department of Medicine, Division of Rheumatology, University of California, San Francisco, CA 94143, USA. 3 Howard Hughes Medical Institute and Department of Medicine and Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA. 4 Cytos Biotechnology AG, Wagisstrasse 25, 8952 Schlieren, Switzerland.
* To whom correspondence should be addressed. E-mail: mueller{at}microbio.emory.edu
The editors suggest the following Related Resources on Science sites:
In Science Magazine
INTRODUCTION TO SPECIAL ISSUE
Stephen J. Simpson and John Travis (3 August 2007) Science317 (5838), 611.
[DOI: 10.1126/science.317.5838.611] |Summary »|PDF »
In Science Signaling
EDITORS' CHOICE
Stephen J. Simpson (7 August 2007) Sci. STKE2007 (398), tw285.
[DOI: 10.1126/stke.3982007tw285] |Abstract »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
IFN-{gamma} and STAT1 Arrest Monocyte Migration and Modulate RAC/CDC42 Pathways.
Y. Hu, X. Hu, L. Boumsell, and L. B. Ivashkiv (2008)
J. Immunol.
180, 8057-8065
|Abstract »|Full Text »|PDF »
Coordination of Early Protective Immunity to Viral Infection by Regulatory T Cells.
J. M. Lund, L. Hsing, T. T. Pham, and A. Y. Rudensky (2008)
Science
320, 1220-1224
|Abstract »|Full Text »|PDF »
Ly49H+ NK Cells Migrate to and Protect Splenic White Pulp Stroma from Murine Cytomegalovirus Infection.
V. Bekiaris, O. Timoshenko, T. Z. Hou, K. Toellner, S. Shakib, F. Gaspal, F. M. McConnell, S. M. Parnell, D. Withers, C. D. Buckley, et al. (2008)
J. Immunol.
180, 6768-6776
|Abstract »|Full Text »|PDF »
Nonoverlapping Expression of IL10, IL12p40, and IFN{gamma} mRNA in the Marginal Zone and T Cell Zone of the Spleen after Antigenic Stimulation.
K. Kalies, P. Konig, Y.-M. Zhang, M. Deierling, J. Barthelmann, C. Stamm, and J. Westermann (2008)
J. Immunol.
180, 5457-5465
|Abstract »|Full Text »|PDF »
Enhancing therapeutic vaccination by blocking PD-1-mediated inhibitory signals during chronic infection.
S.-J. Ha, S. N. Mueller, E. J. Wherry, D. L. Barber, R. D. Aubert, A. H. Sharpe, G. J. Freeman, and R. Ahmed (2008)
J. Exp. Med.
205, 543-555
|Abstract »|Full Text »|PDF »
Differential Microenvironment Localization of Effector and Memory CD8 T Cells.
J. G. Dauner, I. R. Williams, and J. Jacob (2008)
J. Immunol.
180, 291-299
|Abstract »|Full Text »|PDF »
. This modulation was found to alter the localization of lymphocytes and dendritic cells within responding lymphoid tissues. As a consequence, priming of T cell responses to a second distinct pathogen after chemokine modulation became impaired. We propose that this transient chemokine modulation may help orchestrate local cellularity, thus minimizing competition for space and resources in activated lymphoid tissues. 
