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Journal of Virology, May 2006, p. 5032-5040, Vol. 80, No. 10
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.10.5032-5040.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Alpha and Lambda Interferon Together Mediate Suppression of CD4 T Cells Induced by Respiratory Syncytial Virus

Bo Chi,1 Harold L. Dickensheets,2 Kirsten M. Spann,3 Marc A. Alston,1 Cindy Luongo,3 Laure Dumoutier,4 Jiaying Huang,5 Jean-Christophe Renauld,4 Sergei V. Kotenko,5 Mario Roederer,3 Judy A. Beeler,1 Raymond P. Donnelly,2 Peter L. Collins,3 and Ronald L. Rabin1*

Center for Biologics Evaluation and Research,1 Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Bethesda, Maryland,2 National Institute of Allergy and Infectious Diseases, Bethesda, Maryland,3 Ludwig Institute for Cancer Research, Brussels Branch, and Experimental Medicine Unit, Université de Louvain, Brussels, Belgium,4 Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey5

Received 4 November 2005/ Accepted 21 February 2006

The mechanism by which respiratory syncytial virus (RSV) suppresses T-cell proliferation to itself and other antigens is poorly understood. We used monocyte-derived dendritic cells (MDDC) and CD4 T cells and measured [3H]thymidine incorporation to determine the factors responsible for RSV-induced T-cell suppression. These two cell types were sufficient for RSV-induced suppression of T-cell proliferation in response to cytomegalovirus or Staphylococcus enterotoxin B. Suppressive activity was transferable with supernatants from RSV-infected MDDC and was not due to transfer of live virus or RSV F (fusion) protein. Supernatants from RSV-infected MDDC, but not MDDC exposed to UV-killed RSV or mock conditions, contained alpha interferon (IFN-{alpha}; median, 43 pg/ml) and IFN-{lambda} (approximately 1 to 20 ng/ml). Neutralization of IFN-{alpha} with monoclonal antibody (MAb) against one of its receptor chains, IFNAR2, or of IFN-{lambda} with MAb against either of its receptor chains, IFN-{lambda}R1 (interleukin 28R [IL-28R]) or IL-10R2, had a modest effect. In contrast, blocking the two receptors together markedly reduced or completely blocked the RSV-induced suppression of CD4 T-cell proliferation. Defining the mechanism of RSV-induced suppression may guide vaccine design and provide insight into previously uncharacterized human T-cell responses and activities of interferons.

* Corresponding author. Mailing address: Center for Biologics Evaluation and Research, 29 Lincoln Drive, Room B1, Bethesda, MD 20892. Phone: (301) 496-8806. Fax: (301) 402-5177. E-mail: rrabin{at}helix.nih.gov.

Journal of Virology, May 2006, p. 5032-5040, Vol. 80, No. 10
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.10.5032-5040.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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