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首页> 外文期刊>Journal of immunotherapy >In vitro generation of Epstein-Barr virus-specific cytotoxic T cells in patients receiving haplo-identical allogeneic stem cell transplantation.
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In vitro generation of Epstein-Barr virus-specific cytotoxic T cells in patients receiving haplo-identical allogeneic stem cell transplantation.

机译：在接受单倍相同的同种异体干细胞移植的患者中，爱泼斯坦-巴尔病毒特异性细胞毒性T细胞的体外生成。

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Use of a partially mismatched related donor (PMRD) is an option for patients who require allogeneic transplantation but do not have a matched sibling or unrelated donor. Epstein-Barr virus (EBV)-induced lymphoma is a major cause of mortality after PMRD transplantation. In this study, we present a clinical grade culture system for donor-derived EBV-specific cytotoxic T cells (CTLs) that do not recognize haplo-identical recipient cells. The EBV-specific CTLs were tested for cytolytic specificity and other functional properties, including ability to transgress into tissues, propensity for apoptosis, degree of clonality, stability of dominant T-cell clones, and Tc and Th phenotypes. The EBV-specific CTLs were routinely expanded to greater than 80 x 10(6) over a period of 5 weeks, which is sufficient for clinical application. A CD8+ phenotype predominated, and the CTLs were highly specific for donor lymphoblastoid cell lines (LCLs) without killing of recipient targets or K562. Vbeta spectratyping showed an oligoclonal population that was stable on prolonged culture. The EBV-specific CTLs were activated (D-related human leukocyte antigen [HLA-DR+], L-selectin+/-) and of memory phenotype (CD45RO+). Expression of the integrin VLA-4 suggested that these CTLs could adhere to endothelium and migrate into tissues. The Bcl-2 message was upregulated, which may protect the CTLs from the apoptosis. The first demonstration of overexpression of bcl-2 in human memory CTLs. In addition, we show that lymphoblastoid cell lines used to generate CTLs are readily genetically modified with recombinant lentivirus, indicating that genetically engineered antigen presentation is feasible.
机译：对于需要同种异体移植但没有匹配的同胞或不相关供体的患者，可以选择使用部分不匹配的相关供体（PMRD）。爱泼斯坦巴尔病毒（EBV）引起的淋巴瘤是PMRD移植后导致死亡的主要原因。在这项研究中，我们为不识别单倍体相同受体细胞的供体来源的EBV特异性细胞毒性T细胞（CTL）提供了一种临床级培养系统。测试了EBV特异性CTL的溶细胞特异性和其他功能特性，包括进入组织的能力，凋亡倾向，克隆程度，优势T细胞克隆的稳定性以及Tc和Th表型。 EBV特异性CTL通常在5周内扩展到大于80 x 10（6），足以用于临床。 CD8 +表型为主​​，并且CTL对供体淋巴母细胞系（LCL）具有高度特异性，而不会杀死受体靶标或K562。 Vbeta谱型显示在长期培养中稳定的寡克隆种群。激活了EBV特异性CTL（D相关人白细胞抗原[HLA-DR +]，L-选择素+/-）并具有记忆表型（CD45RO +）。整联蛋白VLA-4的表达表明这些CTL可以粘附于内皮并迁移到组织中。 Bcl-2信息被上调，这可能保护CTL免受凋亡。人类记忆CTL中bcl-2过表达的第一个证明。此外，我们显示用于生成CTL的淋巴母细胞系很容易用重组慢病毒进行基因修饰，表明基因工程抗原呈递是可行的。

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