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Blood, 15 November 2006, Vol. 108, No. 10, pp. 3253-3261. Prepublished online as a Blood First Edition Paper on July 25, 2006; DOI 10.1182/blood-2006-06-027599. This Article Full Text (PDF) All Versions of this Article: blood-2006-06-027599v1 108/10/3253    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 Kamphuis, E. Articles by Kalinke, U. Search for Related Content PubMed PubMed Citation Articles by Kamphuis, E. Articles by Kalinke, U. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 17, 2006 Accepted July 4, 2006 Type I interferons directly regulate lymphocyte recirculation and cause transient blood lymphopenia Elisabeth Kamphuis, Tobias Junt, Zoe Waibler, Reinhold Forster, and Ulrich Kalinke* Paul-Ehrlich-Institut, Division of Immunology, Langen, Germany CBR Institute for Biomedical Research & Department of Pathology, Harvard Medical School, MA, USA Hannover Medical School, Institute of Immunology, Hannover, Germany * Corresponding author; email: kalul{at}pei.de. Early viral infection is often associated with lymphopenia, a transient reduction of blood lymphocyte counts long before onset of clinical symptoms. We have investigated lymphopenia in mice infected with vesicular stomatitis virus (VSV) or treated with the Toll-like receptor (TLR) agonists poly(I:C) and R-848. In all cases analyzed, lymphopenia was critically dependent on type I interferon receptor (IFNAR) signaling. Using bone marrow-chimeric mice, radio-resistant cells, such as stroma and endothelium, could be excluded as type I interferon (IFN-/) targets for the induction of lymphopenia. Instead, adoptive transfer experiments and studies in conditionally gene-targeted mice with a B or T cell-specific IFNAR deletion demonstrated that IFN-/ exerted a direct effect on lymphocytes that was necessary and largely sufficient to induce lymphopenia. Furthermore, following treatment with R-848 we found that other cytokines such as TNF- also played a role in T cell lymphopenia. Investigation of the molecular mechanism revealed that lymphopenia was mainly independent of G protein-coupled receptors (GPCRs) and chemokines. In an adhesion assay, B cells of poly(I:C)-treated mice showed moderately increased adhesion to ICAM-1, but not to VCAM- 1. In conclusion, our data identify a new effect of direct IFN-/ stimulation of lymphocytes that profoundly affects lymphocyte redistribution. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Stoltz, C. Ahlm, A. Lundkvist, and J. Klingstrom Lambda Interferon (IFN-{lambda}) in Serum Is Decreased in Hantavirus-Infected Patients, and In Vitro-Established Infection Is Insensitive to Treatment with All IFNs and Inhibits IFN-{gamma}-Induced Nitric Oxide Production J. Virol., August 15, 2007; 81(16): 8685 - 8691. [Abstract] [Full Text] [PDF] P. Bach, E. Kamphuis, B. Odermatt, G. Sutter, C. J. Buchholz, and U. Kalinke Vesicular Stomatitis Virus Glycoprotein Displaying Retrovirus-Like Particles Induce a Type I IFN Receptor-Dependent Switch to Neutralizing IgG Antibodies J. Immunol., May 1, 2007; 178(9): 5839 - 5847. [Abstract] [Full Text] [PDF]

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