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, JY, Renauld, JC, Kotenko, SV, Roederer, M, Beeler, JA, Donnelly, RP, Collins, PL and Rabin, RL (2006) Alpha and lambda interferon together mediate suppression of CD4 T cells induced by respiratory syncytial virus. Journal of Virology, 80 10: 5032-5040.


Author(s) Chi, B
Dickensheets, HL
Spann, KM
Alston, MA
Luongo, C
Dumoutier, L
Huang, JY
Renauld, JC
Kotenko, SV
Roederer, M
Beeler, JA
Donnelly, RP
Collins, PL
Rabin, RL
Title Alpha and lambda interferon together mediate suppression of CD4 T cells induced by respiratory syncytial virus
Journal name Journal of Virology
Publication date 2006
Sub-type Article
Volume number 80
Issue number 10
ISSN 0022-538X
Start page 5032
End page 5040
Total pages 9
Place of publication Washington
Publisher Amer Soc Microbiology
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 [H-3]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.
Keyword(s) Virology
Interleukin-1 Inhibitor Production
Nonstructural Proteins Ns1
Dendritic Cells
Parainfluenza Virus
Epithelial-cells
Viral-infection
Influenza-virus
Pasteurella-haemolytica
Lymphocyte-responses
Regulatory Factor-3
 
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