Allo-HLA reactivity of virus-specific memory T cells is common
Allo-HLA reactivity of virus-specific memory T cells is common
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DOI：
10.1182/blood-2009-07-234906
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发表时间：
2010-04-15
期刊：
影响因子：
20.3
通讯作者：
Heemskerk, Mirjam H. M.
中科院分区：
文献类型：
--
作者：
Amir, Avital L.;D'Orsogna, Lloyd J. A.;Heemskerk, Mirjam H. M.
移植物抗宿主病和移植物排斥反应是由同种异体反应性T细胞引起的异基因血型不合干细胞移植或器官移植的主要并发症。由于一系列急性病毒感染与这些并发症的发生有关，我们假设病毒特异性记忆T细胞与同种(Allo)人类白细胞抗原(Allo)分子的交叉反应可能能够介导这些并发症。为了分析异基因人类白细胞抗原的反应性，对EB病毒、巨细胞病毒、水痘带状疱疹病毒和流感病毒的特异性T细胞与一组人类白细胞抗原(HLA型)靶细胞进行了对照，并用单一的人类白细胞抗原分子转导靶细胞。80%的T细胞株和45%的病毒特异性T细胞克隆被证明与allo-HLA分子发生交叉反应。CD8和CD4T细胞克隆的交叉反应主要针对人类白细胞抗原I类和II类。T细胞受体(TCR)基因转移证实了Alo-HLA反应性和病毒特异性是通过相同的TCR介导的。这些结果表明，相当大比例的病毒特异性T细胞具有异基因-人类白细胞抗原反应性，这可能对移植环境以及第三方病毒特异性T细胞的过继转移具有重要的临床意义。(血。2010；115(15)：3146-3157)
Graft-versus-host disease and graft rejection are major complications of allogeneic HLA-mismatched stem cell transplantation or organ transplantation that are caused by alloreactive T cells. Because a range of acute viral infections have been linked to initiating these complications, we hypothesized that the cross-reactive potential of virus-specific memory T cells to allogeneic (allo) HLA molecules may be able to mediate these complications. To analyze the allo-HLA reactivity, T cells specific for Epstein-Barr virus, cytomegalovirus, varicella zoster virus, and influenza virus were tested against a panel of HLA-typed target cells, and target cells transduced with single HLA molecules. Eighty percent of T-cell lines and 45% of virus-specific T-cell clones were shown to cross-react against allo-HLA molecules. The cross-reactivity of the CD8 and CD4 T-cell clones was directed primarily against HLA class I and II, respectively. However, a restricted number of CD8 T cells exhibited cross-reactivity to HLA class II. T-cell receptor (TCR) gene transfer confirmed that allo-HLA reactivity and virus specificity were mediated via the same TCR. These results demonstrate that a substantial proportion of virus-specific T cells exert allo-HLA reactivity, which may have important clinical implications in transplantation settings as well as adoptive transfer of third-party virus-specific T cells. (Blood. 2010;115(15):3146-3157)