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

Author

UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique, Chi, Bo, Dickensheets, Harold L, Spann, Kirsten M, Alston, Marc A, Luongo, Cindy, Dumoutier, Laure, Huang, Jiaying, Renauld, Jean-Christophe, Kotenko, Sergei V, Roederer, Mario, Beeler, Judy A, Donnelly, Raymond P, Collins, Peter L, Rabin, Ronald L, UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique, Chi, Bo, Dickensheets, Harold L, Spann, Kirsten M, Alston, Marc A, Luongo, Cindy, Dumoutier, Laure, Huang, Jiaying, Renauld, Jean-Christophe, Kotenko, Sergei V, Roederer, Mario, Beeler, Judy A, Donnelly, Raymond P, Collins, Peter L, and Rabin, Ronald L

Abstract

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.

Published
2006

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

Author

Chi, Bo, primary, Dickensheets, Harold L., additional, Spann, Kirsten M., additional, Alston, Marc A., additional, Luongo, Cindy, additional, Dumoutier, Laure, additional, Huang, Jiaying, additional, Renauld, Jean-Christophe, additional, Kotenko, Sergei V., additional, Roederer, Mario, additional, Beeler, Judy A., additional, Donnelly, Raymond P., additional, Collins, Peter L., additional, and Rabin, Ronald L., additional

Published
2006
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12. Alpha and Lambda Interferon Together Mediate Suppression of CD4 T Cells Induced by Respiratory Syncytial Virus.

Author

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

Subjects
*RESPIRATORY syncytial virus, *T cells, *ANTIGENS, *DENDRITIC cells, *THYMIDINE
Abstract

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-α; median, 43 pg/ml) and IFN-λ (approximately 1 to 20 ng/ml). Neutralization of IFN-α with monoclonal antibody (MAb) against one of its receptor chains, IFNAR2, or of IFN-λ with MAb against either of its receptor chains, IFN-λR1 (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. [ABSTRACT FROM AUTHOR]

Published
2006
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