Kim Sang-Ki, Nguyen Pham Thanh-Nhan, Nguyen Hoang Tuyet Minh, Kang Hyun-Kyu, Jin Chun-Ji, Nam Jong-Hee, Chung Sang-Young, Choi So-Jin-Na, Yang Deok-Hwan, Kim Yeo-Kyeoung, Chung Ik-Joo, Kim Hyeoung-Joon, Lee Je-Jung
Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Jeonnam, South Korea.
Ann Hematol. 2009 Nov;88(11):1113-23. doi: 10.1007/s00277-009-0721-y. Epub 2009 Mar 11.
We investigated to establish CD40-activated B cells (CD40-B cells) as alternative antigen-presenting cells (APCs) for the induction of myeloma-specific cytotoxic T lymphocytes (CTLs). To generate CD40-B cells, peripheral blood mononuclear cells were co-cultured with CD40L-transfected J558 cells in the presence of IL-4, insulin, transferrin, and cyclosporine for 14 days, and pulsed with myeloma lysates. The CD40-B cells consistently expressed high levels of CD80, CD86, CD54, CCR7, and HLA-DR. The CD40-B cells produced IL-12, IFN-gamma, and IL-6 during the culture period, but not IL-10. In addition, the CD40-B cells showed potent allogeneic T-cell stimulatory capacities that depended on the dose ratio and had the potential to polarize naïve T cells into Th1 subsets. The CD40-B cells loaded with tumor lysates induced strong target-specific CTLs, based on large numbers of IFN-gamma secreting cells and higher cytotoxic activity against target cells compared to the CD40-B cells without the tumor lysates. These results suggest that CD40-B cells loaded with myeloma lysates might provide alternative APCs for cellular immunotherapy in patients with myeloma.
我们进行研究以确立经CD40激活的B细胞（CD40 - B细胞）作为诱导骨髓瘤特异性细胞毒性T淋巴细胞（CTL）的替代抗原呈递细胞（APC）。为了生成CD40 - B细胞，将外周血单个核细胞与转染了CD40L的J558细胞在白细胞介素-4、胰岛素、转铁蛋白和环孢素存在的情况下共培养14天，并用骨髓瘤裂解物脉冲处理。CD40 - B细胞持续高水平表达CD80、CD86、CD54、CCR7和HLA - DR。在培养期间，CD40 - B细胞产生白细胞介素-12、干扰素-γ和白细胞介素-6，但不产生白细胞介素-10。此外，CD40 - B细胞表现出强大的同种异体T细胞刺激能力，这取决于剂量比，并且有潜力将幼稚T细胞极化为Th1亚群。与未加载肿瘤裂解物的CD40 - B细胞相比，加载肿瘤裂解物的CD40 - B细胞基于大量分泌干扰素-γ的细胞以及对靶细胞更高的细胞毒性活性，诱导出强大的靶标特异性CTL。这些结果表明，加载骨髓瘤裂解物的CD40 - B细胞可能为骨髓瘤患者的细胞免疫治疗提供替代的APC。
