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IL-21、IL-7 和 IL-15 条件培养基在扩增健康供体-PBMC 中抗原特异性 CD8+T 细胞中的应用,适用于免疫治疗。

Usefulness of IL-21, IL-7, and IL-15 conditioned media for expansion of antigen-specific CD8+ T cells from healthy donor-PBMCs suitable for immunotherapy.

机构信息

Immunology and Translational Medicine Research Group, Department of Microbiology, School of Medicine, Universidad Nacional de Colombia, Carrera 30 No. 45-03, Bogotá, South-America, Colombia; Immunology and Clinical Oncology Research Group, Fundación Salud de los Andes, Calle 44 #58-05, Bogotá, South-America, Colombia.

Immunology and Clinical Oncology Research Group, Fundación Salud de los Andes, Calle 44 #58-05, Bogotá, South-America, Colombia.

出版信息

Cell Immunol. 2021 Feb;360:104257. doi: 10.1016/j.cellimm.2020.104257. Epub 2020 Dec 14.

DOI:10.1016/j.cellimm.2020.104257
PMID:33387685
Abstract

Clonal anergy and depletion of antigen-specific CD8+ T cells are characteristics of immunosuppressed patients such as cancer and post-transplant patients. This has promoted translational research on the adoptive transfer of T cells to restore the antigen-specific cellular immunity in these patients. In the present work, we compared the capability of PBMCs and two types of mature monocyte-derived DCs (moDCs) to prime and to expand ex-vivo antigen-specific CD8+ T cells using culture conditioned media supplemented with IL-7, IL-15, and IL-21. The data obtained suggest that protocols involving moDCs are as efficient as PBMCs-based cultures in expanding antigen-specific CD8+ T cell to ELA and CMV model epitopes. These three gamma common chain cytokines promote the expansion of naïve-like and central memory CD8+ T cells in PBMCs-based cultures and the expansion of effector memory T cells when moDCs were used. Our results provide new insights into the use of media supplemented with IL-7, IL-15, and IL-21 for the in-vitro expansion of early-differentiated antigen-specific CD8+ T cells for immunotherapy purposes.

摘要

克隆性无应答和抗原特异性 CD8+T 细胞耗竭是免疫抑制患者(如癌症和移植后患者)的特征。这促进了 T 细胞过继转移以恢复这些患者的抗原特异性细胞免疫的转化研究。在本工作中,我们比较了外周血单核细胞(PBMC)和两种成熟单核细胞来源的树突状细胞(moDC)在补充了 IL-7、IL-15 和 IL-21 的条件培养基中体外刺激和扩增抗原特异性 CD8+T 细胞的能力。获得的数据表明,涉及 moDC 的方案与基于 PBMC 的培养方案一样高效,可将抗原特异性 CD8+T 细胞扩增至 ELA 和 CMV 模型表位。这三种γ共同链细胞因子促进了基于 PBMC 的培养中初始样和中央记忆 CD8+T 细胞的扩增,以及使用 moDC 时效应记忆 T 细胞的扩增。我们的结果为使用补充了 IL-7、IL-15 和 IL-21 的培养基体外扩增用于免疫治疗目的的早期分化的抗原特异性 CD8+T 细胞提供了新的见解。

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