细胞毒性T淋巴细胞治疗人巨细胞病毒感染在造血干细胞移植中的应用

Application of Cytotoxic T-Lymphocytes for the Treatment of Cytomegalovirus Infection in Hematopoietic Stem Cell Transplantation

人巨细胞病毒(human cytomegalovirus,HCMV)感染是造血干细胞移植后的常见并发症,是造成移植后患者死亡的主要原因之一。细胞毒性T淋巴细胞(cytotoxic T lymphocytes,CTL)是控制HCMV感染的重要免疫细胞,过继输注病毒特异性CTL对预防及治疗HCMV感染均安全有效。目前针对HCMV特异性CTL的制备方法仍在探索中。利用抗原递呈细胞刺激外周血单个核细胞(peripheral blood mononuclear cells,PBMC)制备CTL的方法操作简单,易于开展大规模临床实验;利用肽特异性四聚体或病毒特异性γ-干扰素抗体直接从供者PBMC筛选CTL的方法需要大量的供者外周血,且制备成本高;第三方CTL作为一种产品可以随时使用,但仍需解决HLA不相合的问题。另外,不同方法的临床疗效及安全性也存在差异。本文对目前采用的制备HCMV特异性T淋巴细胞的方法及其疗效进行综述。

Human cytomegalovirus(HCMV) infection,a common complication,remains a major risk factor related with patient death after hematopoietic stem cell transplantation(HSCT).Cytotoxic T lymphocytes(CTL) which is crucial to control HCMV infection,can prevent or treat HCMV infection safely and effectively after adoptive infusion.Many studies have been focussed on exploring different methods for preparation of CTL.The method of using antigen presenting cells to stimulate peripheral blood mononuclear cells is simple to operate,easy to conduct large-scale clinical trials.Isolation of CTL from donor- derived PBMC by peptide- tetramer or INF-γ antibody requires a large volume of peripheral blood and high cost for preparation.Third-party CTL can provide an ' off- the- shelf' product,but the problem of HLAmismatch still would be solved.In addition,the clinical efficacy and safety of different methods also vary.This article reviews and compares the current methods to generate CTL and efficacy of the cells after infusions.