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Blood, 1 October 2005, Vol. 106, No. 7, pp. 2424-2432. Prepublished online as a Blood First Edition Paper on June 23, 2005; DOI 10.1182/blood-2005-01-0342. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: 2005-01-0342v1 106/7/2424    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gunzer, M. Articles by Grabbe, S. Search for Related Content PubMed PubMed Citation Articles by Gunzer, M. Articles by Grabbe, S. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 25, 2005 Accepted June 3, 2005 Systemic administration of a TLR7 ligand leads to transient immune incompetence due to peripheral blood leukocyte depletion Matthias Gunzer*, Helge Riemann, Yasmin Basoglu, Anja Hillmer, Carsten Weishaupt, Sandra Balkow, Bernd Benninghoff, Beat Ernst, Meike Steinert, Thomas Scholzen, Cord Sunderkotter, and Stephan Grabbe German Research Centre for Biotechnology, Braunschweig, Germany; Department of Dermatology, University of Munster, Munster, Germany Department of Dermatology, University of Munster, Munster, Germany German Research Centre for Biotechnology, Braunschweig, Germany 3M Medica GmbH, Neuss, Germany University of Basel Institute of Molecular Pharmacy, Basel, Switzerland Department of Dermatology, University of Munster, Munster, Germany; Department of Dermatology, University of Essen, Essen, Germany * Corresponding author; email: mgunzer{at}gbf.de. Toll-like receptor (TLR) ligands lead to the induction of pro-inflammatory cytokines and are potent enhancers of specific immune responses. We show here that a single systemic dose of R-848, a ligand for TLR7, potently enhanced hapten sensitization during the induction of contact hypersensitivity (CHS). However, R-848 administration also resulted in a rapid and almost complete depletion of leukocytes from the blood. This effect was transient and was associated with general induction of endothelial adhesiveness. In response to R-848 endothelial cells up-regulated adhesion molecules in vitro and in vivo and leukocytes exhibited increased rolling on endothelia in R-848 treated animals. Adhesion molecule induction appeared to be a direct effect, since endothelial cells expressed TLR7 in vitro and in vivo. After R-848 treatment, the tissue residence time of leukocytes was markedly prolonged in all major peripheral organs. The resulting transiently reduced availability of PBL (TRAP) significantly inhibited otherwise potent CHS responses until the effector cells returned. Thus, although TLR7 ligands are effective adjuvants for the induction of cell mediated immunity, they can transiently inhibit the elicitation of localized immune responses, possibly due to a systemic endothelial activation throughout the vasculature. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Baenziger, M. Heikenwalder, P. Johansen, E. Schlaepfer, U. Hofer, R. C. Miller, S. Diemand, K. Honda, T. M. Kundig, A. Aguzzi, et al. Triggering TLR7 in mice induces immune activation and lymphoid system disruption, resembling HIV-mediated pathology Blood, January 8, 2009; 113(2): 377 - 388. [Abstract] [Full Text] [PDF] E. L. J. M. Smits, P. Ponsaerts, Z. N. Berneman, and V. F. I. 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