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This Article Full Text Full Text (PDF) All Versions of this Article: jimmunol.0900252v1 183/3/1990    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Rygiel, T. P. Articles by Meyaard, L. PubMed PubMed Citation Articles by Rygiel, T. P. Articles by Meyaard, L.

Lack of CD200 Enhances Pathological T Cell Responses during Influenza Infection¹

Tomasz P. Rygiel^2,*, Eva S. K. Rijkers^2,*, Talitha de Ruiter^*, Ellen H. Stolte^*, Martin van der Valk, Guus F. Rimmelzwaan, Louis Boon, Anton M. van Loon^¶, Frank E. Coenjaerts^¶, Robert M. Hoek^||, Kiki Tesselaar^* and Linde Meyaard^3,*

^* Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands; Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands; Bioceros, Utrecht, The Netherlands; ^¶ Department of Virology, University Medical Center Utrecht, Utrecht, The Netherlands; ^|| Department of Experimental Immunology, University Medical Center, Amsterdam, The Netherlands

Influenza virus infection can be accompanied by life-threatening immune pathology most likely due to excessive antiviral responses. Inhibitory immune receptors may restrain such overactive immune responses. To study the role of the inhibitory immune receptor CD200R and its ligand CD200 during influenza infection, we challenged wild-type and CD200^–/– mice with influenza virus. We found that CD200^–/– mice in comparison to wild-type controls when inoculated with influenza virus developed more severe disease, associated with increased lung infiltration and lung endothelium damage. CD200^–/– mice did develop adequate adaptive immune responses and were able to control viral load, suggesting that the severe disease was caused by a lack of control of the immune response. Interestingly, development of disease was completely prevented by depletion of T cells before infection, despite dramatically increased viral load, indicating that T cells are essential for the development of disease symptoms. Our data show that lack of CD200-CD200R signaling increases immune pathology during influenza infection, which can be reduced by T cell depletion.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Grant 015.001.070 from The Netherlands Organization for Scientific Research (NWO) (to E.S.K.R.), Grant 07-0086 from The Association for International Cancer Research (AICR) (to T.R.), and Grant 187 from the VanderEs foundation (to E.H.S.).

² T.P.R. and E.S.K.R. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Linde Meyaard, Department of Immunology, University Medical Center Utrecht, Lundlaan 6, Room KC02.085.2, 3584 EA Utrecht, The Netherlands. E-mail address l.meyaard{at}umcutrecht.nl

⁴ Abbreviations used in this paper: DC, dendritic cell; BAL, bronchoalveolar lavage; NP, nucleoprotein; PD-1, programmed death-1; TCID, tissue culture-infective dose; WT, wild type.