Functionally active virus-specific T cells that target CMV, adenovirus, and EBV can be expanded from naive T-cell populations in cord blood and will target a range of viral epitopes
Functionally active virus-specific T cells that target CMV, adenovirus, and EBV can be expanded from naive T-cell populations in cord blood and will target a range of viral epitopes
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DOI：
10.1182/blood-2009-03-213256
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发表时间：
2009-08-27
期刊：
影响因子：
20.3
通讯作者：
Bollard, Catherine M.
中科院分区：
文献类型：
--
作者：
Hanley, Patrick J.;Cruz, Conrad Russell Young;Bollard, Catherine M.
脐带血（CB） T细胞的幼稚表型可能会减少脐带血移植后的移植物抗宿主病，但这种幼稚和它们的低绝对数量也会延迟免疫重建，产生更高的感染相关死亡率，主要与巨细胞病毒、腺病毒（Adv）和EBV有关。采用外周血源性病毒特异性细胞毒性T淋巴细胞（ctl）的过继免疫治疗可以有效地预防常规干细胞移植后的病毒性疾病，我们现在描述了从CB中产生对多种病毒特异性的ctl的单培养。使用临床级Ad5f35CMVpp65腺病毒载体转导的EBV感染的B细胞作为EBV、Adv和CMV抗原的来源，我们甚至从具有初始表型的CB T细胞中扩增出病毒特异性T细胞。扩增后，每个CTL培养都含有CD8（+）和CD4(+) t细胞亚群，主要是效应记忆表型。每个CTL培养物也具有针对EBV、CMV和Adv目标的hla限制性病毒特异性细胞毒效应功能。CB ctl识别多种病毒表位，包括CD4限制性Adv-hexon表位和免疫亚显性CD4和cd8限制性CMVpp65表位。尽管它们的初始表型，因此有可能在CB的单一培养中产生三病毒特异性ctl，这可能对预防或治疗CB移植受者的病毒性疾病有价值。本研究注册于www.clinicaltrials.gov，编号为NCT00078533。（《血液》，2009;114:1958-1967）
The naive phenotype of cord blood (CB) T cells may reduce graft-versus-host disease after umbilical cord blood transplantation, but this naivety and their low absolute numbers also delays immune reconstitution, producing higher infection-related mortality that is predominantly related to CMV, adenovirus (Adv), and EBV. Adoptive immunotherapy with peripheral blood-derived virus-specific cytotoxic T lymphocytes (CTLs) can effectively prevent viral disease after conventional stem cell transplantation, and we now describe the generation of single cultures of CTLs from CB that are specific for multiple viruses. Using EBV-infected B cells transduced with a clinical-grade Ad5f35CMVpp65 adenoviral vector as sources of EBV, Adv, and CMV antigens, we expanded virus-specific T cells even from CB T cells with a naive phenotype. After expansion, each CTL culture contained both CD8(+) and CD4(+) T-cell subsets, predominantly of effector memory phenotype. Each CTL culture also had HLA-restricted virus-specific cytotoxic effector function against EBV, CMV, and Adv targets. The CB CTLs recognized multiple viral epitopes, including CD4-restricted Adv-hexon epitopes and immunosubdominant CD4- and CD8-restricted CMVpp65 epitopes. Notwithstanding their naive phenotype, it is therefore possible to generate trivirus-specific CTLs in a single culture of CB, which may be of value to prevent or treat viral disease in CB transplant recipients. This study is registered at www.clinicaltrials.gov as NCT00078533. (Blood. 2009; 114: 1958-1967)