Park Jung-Yong, Yoon Sung Hee, Kim Eun-Kyung, Yun Sun-Ok, Park Mi-Young, Sohn Hyun-Jung, Kim Tai-Gyu
Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
Immunol Lett. 2008 Feb 15;116(1):33-40. doi: 10.1016/j.imlet.2007.11.005. Epub 2007 Dec 3.
CD40-activated B (CD40-B) cells might be an attractive source of autologous antigen-presenting cells (APCs) for immunotherapy due to the ability to obtain them from peripheral blood and expand them in vitro. However, soluble IL-4 (sIL-4) in B-cell culture may not represent the "immunological synapse" between B and CD4+ T cells. In this study, the K562 cell line, which expresses CD40L and membrane-bound IL-4 (mbIL-4), could induce higher B-cell proliferation and antigen-presenting surface molecules, including adhesion, costimulatory and HLA molecules, compared with sIL-4. The differentiation to plasmablasts was decreased in CD40-B cells treated with mbIL-4 (CD40-B/mbIL-4) based on flow cytometry analysis. Furthermore, CD40-B/mbIL-4 cells were as potent as mature dendritic cells in the allogeneic lymphocyte reaction and the ability to generate cytotoxic T lymphocytes specific for cytomegalovirus pp65 antigen in vitro. Our results suggest that mbIL-4 could be used to generate CD40-B cells as potent APCs for cellular vaccines and adoptive immunotherapy.
由于能够从外周血中获取并在体外扩增，CD40激活的B（CD40 - B）细胞可能是免疫治疗中自体抗原呈递细胞（APC）的一个有吸引力的来源。然而，B细胞培养中的可溶性白细胞介素4（sIL - 4）可能无法代表B细胞与CD4 + T细胞之间的“免疫突触”。在本研究中，表达CD40L和膜结合白细胞介素4（mbIL - 4）的K562细胞系，与sIL - 4相比，能诱导更高的B细胞增殖以及抗原呈递表面分子，包括黏附分子、共刺激分子和HLA分子。基于流式细胞术分析，用mbIL - 4处理的CD40 - B细胞（CD40 - B/mbIL - 4）向浆母细胞的分化减少。此外，CD40 - B/mbIL - 4细胞在同种异体淋巴细胞反应中与成熟树突状细胞一样有效，并且在体外具有产生针对巨细胞病毒pp65抗原的细胞毒性T淋巴细胞的能力。我们的结果表明，mbIL - 4可用于产生CD40 - B细胞，作为细胞疫苗和过继性免疫治疗的有效APC。
