Alpha and lambda interferon together mediate suppression of CD4 T cells induced by respiratory syncytial virus
Alpha and lambda interferon together mediate suppression of CD4 T cells induced by respiratory syncytial virus
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DOI：
10.1128/jvi.80.10.5032-5040.2006
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发表时间：
2006-05-01
影响因子：
5.4
通讯作者：
Rabin, Ronald L.
中科院分区：
文献类型：
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作者：
Chi, Bo;Dickensheets, Harold L.;Rabin, Ronald L.
呼吸道合胞病毒（RSV）抑制T细胞向自身和其他抗原增殖的机制知之甚少。我们使用单核细胞来源的树突状细胞（MDDC）和CD 4 T细胞和测量[H-3]胸苷掺入，以确定负责RSV诱导的T细胞抑制的因素。这两种细胞类型足以抑制RSV诱导的T细胞增殖，以响应巨细胞病毒或葡萄球菌肠毒素B。抑制活性可通过RSV感染MDDC的上清液转移，而不是由于活病毒或RSV F（融合）蛋白的转移。来自RSV感染的MDDC而非暴露于UV杀死的RSV或模拟条件的MDDC的上清液含有α干扰素（IFN-α;中值，43 pg/ml）和IFN-λ（约1至20 ng/ml）。用单克隆抗体（MAb）中和IFN-α的一条受体链IFNAR 2，或用单克隆抗体（MAb）中和IFN-λ的一条受体链IFN-λ R1（白细胞介素28 R [IL-28 R]）或IL-10 R2，具有适度的效果。相反，阻断两种受体一起显着减少或完全阻断RSV诱导的抑制CD 4 T细胞增殖。定义RSV诱导的抑制机制可能指导疫苗设计，并提供对以前未知的人类T细胞反应和干扰素活性的深入了解。
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.