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从脐带血中扩增γδ T细胞:一种治疗可能性。

Expansion of Gammadelta T Cells from Cord Blood: A Therapeutical Possibility.

作者信息

Berglund Sofia, Gaballa Ahmed, Sawaisorn Piamsiri, Sundberg Berit, Uhlin Michael

机构信息

Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.

Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.

出版信息

Stem Cells Int. 2018 Mar 7;2018:8529104. doi: 10.1155/2018/8529104. eCollection 2018.

Abstract

Gammadelta () T cells are found in both blood and tissues and have antiviral and antitumor properties. The frequency of T cells in umbilical cord blood (UCB) is low, and the majority express 1, in contrast to blood, whereas the main subset is δ29 T cells. UCB γδ T cells are functionally immature, which together with their scarcity complicates the development of UCB T cell therapies. We aimed to develop an effective expansion protocol for UCB γ T cells based on zoledronate and IL-2. We found that culture with 5 M zoledronate and 200 IU IL-2/ml medium for 14 days promoted extensive proliferation. The majority of the cultured cells were 92 T cells. The fold expansion of this, originally infrequent, subset was impressive (median and maximum fold change 253 and 1085, resp.). After culture, the cells had a polyclonal T cell repertoire and the main memory subset was central memory (CD45RO CD27). The cells produced cytokines such as IL-1B, IL-2, and IL-8 and displayed significant tumor-killing capacity. These results show that development of expanded UCB T cell therapies is feasible. It could prove a valuable treatment modality for patients after umbilical cord blood transplantation.

摘要

γδ(γδ)T细胞存在于血液和组织中,具有抗病毒和抗肿瘤特性。与血液中的情况相反,脐带血(UCB)中γδT细胞的频率较低,且大多数表达Vγ1,而主要亚群是Vδ2 + γδT细胞。UCB γδT细胞在功能上不成熟,再加上其数量稀少,使得UCB γδT细胞疗法的开发变得复杂。我们旨在基于唑来膦酸和白细胞介素-2(IL-2)开发一种有效的UCB γδT细胞扩增方案。我们发现,用5 μM唑来膦酸和200 IU IL-2/毫升培养基培养14天可促进大量增殖。培养的细胞大多数是Vδ2 + γδT细胞。这个原本稀少的亚群的扩增倍数令人印象深刻(中位数和最大倍数变化分别为253和1085)。培养后,细胞具有多克隆γδT细胞库,主要记忆亚群是中央记忆(CD45RO + CD27 +)。这些细胞产生白细胞介素-1β(IL-1β)、IL-2和IL-8等细胞因子,并表现出显著的肿瘤杀伤能力。这些结果表明,开发扩增的UCB γδT细胞疗法是可行的。它可能被证明是脐带血移植后患者的一种有价值的治疗方式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65c5/5863314/6f1760d34be7/SCI2018-8529104.001.jpg

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