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J Virol 2006 May;80(10):5032-40

Alpha and lambda interferon together mediate suppression of CD4 T cells induced by respiratory syncytial virus.

Chi B, Dickensheets HL, Spann KM, Alston MA, Luongo C, Dumoutier L, Huang J, Renauld JC, Kotenko SV, Roederer M, Beeler JA, Donnelly RP, Collins PL, Rabin RL

Rabin RL, US FDA, Ctr Biol Evaluat & Res, 29 Lincoln Dr,Room B1, Bethesda, MD 20892 USA US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA US FDA, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA NIAID, Bethesda, MD 20892 USA Univ Louvain, Ludwig Inst Canc Res, Brussels Branch, Brussels, Belgium Univ Louvain, Expt Med Unit, Brussels, Belgium Univ Med & Dent New Jersey, Dept Biochem & Mol Biol, New Jersey Med Sch, Newark, NJ USA


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 [(3)H]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-lambdaR1 (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.

Category: Journal Article
PubMed ID: #16641294
Includes FDA Authors from Scientific Area(s): Biologics, Drugs
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29