Type I Interferons Directly Regulate Lymphocyte Recirculation and Cause Transient Blood Lymphopenia.
From: Division of Immunology, Paul-Ehrlich-Institut, Paul-Ehrlich-Str 51-59, D-63225 Langen, Germany.
Blood
- Publish Date: Nov 2006
- ISSN: 0006-4971
- Volume: 108
- Issue: 10
- Pages: 3253-61
- Medium: Print
- Language: English
- Citation (JAMA): Kamphuis Elisabeth, Junt Tobias, Waibler Zoe, et al. Type I Interferons Directly Regulate Lymphocyte Recirculation and Cause Transient Blood Lymphopenia.. Blood Nov 2006;108:3253-61
Abstract
Early viral infection is often associated with lymphopenia, a transient reduction of blood lymphocyte counts long before the 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. With the use of bone marrow-chimeric mice, radioresistant cells, such as stroma and endothelium, could be excluded as type I interferon (IFN-alpha/beta) 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-alpha/beta exerted a direct effect on lymphocytes that was necessary and largely sufficient to induce lymphopenia. Furthermore, after treatment with R-848, we found that other cytokines such as TNF-alpha 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-alpha/beta stimulation of lymphocytes that profoundly affects lymphocyte redistribution.
Mesh Headings (Keywords): Animals, Blood Cells, Cell Adhesion, Cell Adhesion Molecules, Cytokines, Interferon Type I, Lymphocytes, Lymphopenia, Mice, Mice, Knockout, Receptor, Interferon alpha-beta, Signal Transduction, Time Factors, Toll-Like Receptors, Vesicular stomatitis Indiana virus
Check for Full Text / PubMed Unique Identifier (PMID): 16868248
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