Establishment and characterization of a cell based artificial antigen-presenting cell for expansion and activation of CD8+ T cells Ex Vivo
Establishment and characterization of a cell based artificial antigen-presenting cell for expansion and activation of CD8+ T cells Ex Vivo
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DOI：
10.1038/cmi.2008.6
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发表时间：
2008-02-01
影响因子：
24.1
通讯作者：
Pan, Xingyuan
中科院分区：
文献类型：
--
作者：
Gong, Weijuan;Ji, Mingchun;Pan, Xingyuan
预期人工抗原呈递细胞在输注之前刺激T细胞的扩增和获得最佳治疗特征。在此，结合IgG单克隆抗体的可结晶片段的CD 32在人K562白血病细胞上遗传表达，以提供T细胞受体的配体。K562细胞上还表达分别为CD 28和4-1BB的共刺激受体的配体CD 86和4-1BBL。在此基础上，我们将抗CD 3单克隆抗体OKT 3与K32/CD 86/4-1BBL细胞偶联，构建了人工抗原提呈细胞，命名为K32/CD 86/4-1BBL/OKT 3细胞。这些人工修饰的细胞具有诱导CD 8（+）T细胞活化、促进CD 8（+）T细胞增殖、分裂和长期生长、抑制CD 8（+）T细胞凋亡以及增强CD 8（+）T细胞分泌IFN-γ和穿孔素的能力。此外，抗原特异性细胞毒性T淋巴细胞可以在K32/CD 86/4-1BBL/OKT 3细胞刺激的培养物中至少在28天内保留。这种方法对于CD 8（+）T细胞的扩增和活化是稳健的、简单的、可重复的和经济的，并且可能对过继免疫疗法具有重要的治疗意义。
Artificial antigen-presenting cells are expected to stimulate the expansion and acquisition of optimal therapeutic features of T cells before infusion. Here CD32 that binds to a crystallizable fragment of IgG monoclonal antibody was genetically expressed on human K562 leukemia cells to provide a ligand for T-cell receptor. CD86 and 4-1BBL, which are ligands of co-stimulating receptors of CD28 and 4-1BB, respectively, were also expressed on K562 cells. Then we accomplished the artificial antigen-presenting cells by coupling K32/CD86/4-1BBL cell with OKT3 monoclonal antibody against CD3, named K32/CD86/4-1BBL/OKT3 cells. These artificial modified cells had the abilities of inducing CD8(+) T cell activation, promoting CD8(+) T cell proliferation, division, and long-term growth, inhibiting CD8(+) T cell apoptosis, and enhancing CD8(+) T cell secretion of IFN-gamma and perforin. Furthermore, antigen-specific cytotoxic T lymphocytes could be retained in the culture stimulated with K32/CD86/4-1BBL/OKT3 cells at least within 28 days. This approach was robust, simple, reproducible and economical for expansion and activation of CD8(+) T cells and may have important therapeutic implications for adoptive immunotherapy.