Leen Ann M, Sili Uluhan, Savoldo Barbara, Jewell Alan M, Piedra Pedro A, Brenner Malcolm K, Rooney Cliona M
Center for Cell and Gene Therapy, Department of Pediatrics, 6621 Fannin S, MC 3-3320, Houston, TX 77030, USA.
Blood. 2004 Feb 1;103(3):1011-9. doi: 10.1182/blood-2003-07-2449. Epub 2003 Oct 2.
Adenovirus (Ad) infections are responsible for considerable morbidity and mortality, particularly in pediatric hematopoietic stem cell transplant (HSCT) recipients. To date there is no therapy. The present study was motivated by the potential for using adoptive immunotherapy as either prophylaxis or treatment for Ad infections and associated diseases. The authors have developed a protocol to reactivate Ad-specific memory T cells from peripheral blood mononuclear cells (PBMCs) using a clinical-grade adenoviral vector. Such lines contain a specific CD4 and CD8 T-cell component and are capable of recognizing and lysing target cells infected with wild-type Ad serotypes from different Ad groups. Furthermore, the frequency of Ad-specific precursors can be determined in PBMCs ex vivo and used as a means to assess changes in Ad-specific T-cell memory responses after infusion. This is the first report of a simple and reproducible method to activate and expand Ad-specific cytotoxic T lymphocytes (CTLs), which should be protective against the range of different Ad subtypes that affect transplant recipients.
腺病毒（Ad）感染会导致相当高的发病率和死亡率，尤其是在儿科造血干细胞移植（HSCT）受者中。迄今为止，尚无治疗方法。本研究的动机是利用过继性免疫疗法作为预防或治疗腺病毒感染及相关疾病的潜在手段。作者开发了一种方案，使用临床级腺病毒载体从外周血单个核细胞（PBMC）中重新激活腺病毒特异性记忆T细胞。此类细胞系包含特定的CD4和CD8 T细胞成分，能够识别并裂解感染了来自不同腺病毒组的野生型腺病毒血清型的靶细胞。此外，腺病毒特异性前体细胞的频率可在体外的PBMC中测定，并用作评估输注后腺病毒特异性T细胞记忆反应变化的一种手段。这是关于激活和扩增腺病毒特异性细胞毒性T淋巴细胞（CTL）的简单且可重复方法的首次报道，该方法应对影响移植受者的不同腺病毒亚型具有保护作用。
