Affiliation:
1. From the Division of Immunology, Paul-Ehrlich-Institut, Langen, Germany; CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, MA; and Hannover Medical School, Institute of Immunology, Hannover, Germany.
Abstract
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-α/β) 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-α/β 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-α 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-α/β stimulation of lymphocytes that profoundly affects lymphocyte redistribution.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
Reference63 articles.
1. Gresser I, Guy-Grand D, Maury C, Maunoury MT. Interferon induces peripheral lymphadenopathy in mice. J Immunol. 1981;127: 1569-1575.
2. Schattner A, Meshorer A, Wallach D. Involvement of interferon in virus-induced lymphopenia. Cell Immunol. 1983;79: 11-25.
3. Hirsch RL, Johnson KP. The effects of long-term administration of recombinant alpha-2 interferon on lymphocyte subsets, proliferation, and suppressor cell function in multiple sclerosis. J Interferon Res. 1986;6: 171-177.
4. Aulitzky WE, Tilg H, Vogel W, et al. Acute hematologic effects of interferon alpha, interferon gamma, tumor necrosis factor alpha and interleukin 2. Ann Hematol. 1991;62: 25-31.
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