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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
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. 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. 
