Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands.
Transplantation. 2011 Mar 27;91(6):645-51. doi: 10.1097/TP.0b013e318208c071.
Allo-human leukocyte antigen (HLA) reactivity by naturally acquired viral-specific memory T cells is common. However, the effect of successful vaccination on the alloreactive memory T-cell repertoire is unclear. We hypothesized that vaccination could specifically induce allo-HLA-reactive memory T cells.
A varicella-zoster virus (VZV) immediate early 62 (IE62)-specific CD8 memory T-cell clone was single cell sorted from a VZV seronegative renal transplant candidate after response to live attenuated varicella vaccination. To analyze the allo-HLA reactivity, the VZV IE62-specific T-cell clone was tested against HLA-typed target cells and target cells transfected with HLA molecules, in both cytokine production and cytotoxicity assays.
The varicella vaccine-induced VZV IE62-specific T-cell clone specifically produced interferon-γ when stimulated with HLA-B55:01-expressing Epstein-Barr virus-transformed B cells and HLA-B55:01-transfected K562 cells (single HLA antigen expressing cell line [SALs]) only. The clone also demonstrated specific cytolytic effector function against HLA-B55:01 SALs and phytohemagglutinin blasts. Cytotoxicity assays using proximal tubular epithelial cell and human umbilical vein endothelial cell targets confirmed the kidney tissue specificity of the allo-HLA-B55:01 reactivity, and the relevance of the cross-reactivity to clinical kidney transplantation. The results also suggest that molecular mimicry, and not bystander proliferation, is the mechanism underlying vaccine-induced alloreactivity.
Varicella vaccination generated a de novo alloreactive kidney cell-specific cytolytic effector memory T cell in a patient awaiting renal transplantation. Vaccination-induced alloreactivity may have important clinical implications, especially for vaccine timing and recipient monitoring.
自然获得的病毒特异性记忆 T 细胞对异源人类白细胞抗原（HLA）具有反应性是常见的。然而，成功接种疫苗对异源反应性记忆 T 细胞库的影响尚不清楚。我们假设疫苗可以特异性地诱导异源 HLA 反应性记忆 T 细胞。
从对活减毒水痘疫苗有反应的 VZV 血清阴性肾移植候选者中，通过单细胞分选获得水痘带状疱疹病毒（VZV）早期 62（IE62）特异性 CD8 记忆 T 细胞克隆。为了分析异源 HLA 反应性，用 VZV IE62 特异性 T 细胞克隆在细胞因子产生和细胞毒性测定中对 HLA 分型靶细胞和转染 HLA 分子的靶细胞进行测试。
水痘疫苗诱导的 VZV IE62 特异性 T 细胞克隆在刺激表达 HLA-B55:01 的 EBV 转化 B 细胞和 HLA-B55:01 转染 K562 细胞（单一 HLA 抗原表达细胞系[SAL]）时，特异性产生干扰素-γ。该克隆还对 HLA-B55:01 SAL 和植物血球凝集素刺激的原代肾小管上皮细胞和人脐静脉内皮细胞靶细胞显示出特异性细胞毒性效应功能。使用近端肾小管上皮细胞和人脐静脉内皮细胞靶细胞的细胞毒性测定证实了 HLA-B55:01 反应性的肾组织特异性，以及与临床肾移植的交叉反应相关性。结果还表明，分子模拟而不是旁观者增殖是疫苗诱导的同种异体反应的机制。
水痘疫苗在等待肾移植的患者中产生了一种新的异源肾细胞特异性细胞毒性效应记忆 T 细胞。疫苗诱导的同种异体反应可能具有重要的临床意义，特别是在疫苗接种时间和受者监测方面。
