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Science 317 (5838): 670-674

Copyright © 2007 by the American Association for the Advancement of Science

Regulation of Homeostatic Chemokine Expression and Cell Trafficking During Immune Responses

Scott N. Mueller,1* Karoline A. Hosiawa-Meagher,2 Bogumila T. Konieczny,1 Brandon M. Sullivan,3 Martin F. Bachmann,4 Richard M. Locksley,3 Rafi Ahmed,1 Mehrdad Matloubian2

Abstract: The chemokines CCL21 and CXCL13 are immune factors that dictate homing and motility of lymphocytes and dendritic cells in lymphoid tissues. However, the means by which these chemokines are regulated and how they influence cell trafficking during immune responses remain unclear. We show that CCL21 and CXCL13 are transiently down-regulated within lymphoid tissues during immune responses by a mechanism controlled by the cytokine interferon-{gamma}. 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.

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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