Dominant expression of interleukin-10 and transforming growth factor-β genes in activated T-cells of chronic active Epstein-Barr virus infection
Dominant expression of interleukin-10 and transforming growth factor-β genes in activated T-cells of chronic active Epstein-Barr virus infection
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DOI：
10.1002/jmv.20197
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发表时间：
2004-11-01
影响因子：
12.7
通讯作者：
Hara, T
中科院分区：
文献类型：
--
作者：
Ohga, S;Nomura, A;Hara, T
慢性活动性EB病毒（EBV）感染是一种慢性单核细胞增多症综合征，与携带EBV的T细胞/自然杀伤（NK）细胞的克隆性增殖有关。高水平的循环EBV和活化的T细胞在延长的疾病过程中持续存在，而不清楚T-/NK-细胞中的异位EBV感染是如何建立和维持的。为了评估活化T细胞在慢性活动性EBV感染（CAEBV）中的生物学作用，定量CAEBV和传染性单核细胞增多症（IM）患者外周T细胞中的EBV DNA和细胞基因表达。在CAEBV中，HLA-DR+ T细胞比HLA-DR-T细胞具有更高的病毒载量和更大量的IFN γ、IL-10、转化生长因子-β（TGF β）和细胞毒性T淋巴细胞抗原-4（CTLA 4）mRNA。IM患者的HLA-DR+ T细胞比其HLA-DR-T细胞转录更多的IFN γ和IL-10。CAEBV HLA-DR+ T细胞中IFN γ和叉头框p3（Foxp 3）的表达水平高于IM HLA-DR + T细胞。区分HLA-DR阳性的有效变量依次为IL-10、IFNgamma、CTLA 4、TGFbeta和IL-2。CAEBV T细胞中的EBV负荷仅与IL-10和TGF β的表达水平相关。这些结果表明，CAEBV T细胞被激活过度转录IFN γ，IL-10和TGF β，后两个基因在EBV感染的亚群中优先表达。调节性细胞因子在T细胞中的优势表达可能意味着疾病中的病毒逃避机制。(C)2004 Wiley-Liss，Inc.
Chronic active Epstein-Barr virus (EBV) infection is a chronic mononucleosis syndrome associated with clonal proliferation of EBV-carrying T-/natural killer (NK)-cells. High levels of circulating EBV and activated T-cells are sustained during the prolonged disease course, whereas it is not clear how ectopic EBV infection in T-/NK-cells has been established and maintained. To assess the biological role of activated T-cells in chronic active EBV infection (CAEBV), EBV DNA and cellular gene expressions in peripheral T-cells were quantified in CAEBV and infectious mononucleosis (IM) patients. In CAEBV, HLA-DR+ T-cells had higher viral load and larger amounts of IFNgamma, IL-10, transforming growth factor-beta (TGFbeta), and cytotoxic T lymphocyte antigen-4 (CTLA4) mRNA than HLA-DR-T-cells. HLA-DR+ T cells of IM patients transcribed more IFNgamma and IL-10 than their HLA-DR-T cells. Expression levels of IFNgamma and forkhead box p3 (Foxp3) in CAEBV HLA-DR+ T-cells were higher than in IM HLA-DR+ T-cells. The effective variables to discriminate the positivity of HLA-DR were IL-10, IFNgamma, CTLA4, TGFbeta, and IL-2 in the order of statistical weight. EBV load in CAEBV T-cells correlated with the expression levels of only IL-10 and TGFbeta. These results suggest that CAEBV T-cells are activated to transcribe IFNgamma, IL-10, and TGFbeta excessively, and the latter two genes are expressed preferentially in the EBV-infected subsets. The dominant expression of regulatory cytokines in T-cells may imply a viral evasion mechanism in the disease. (C) 2004 Wiley-Liss, Inc.