Xu Qianghua, Katakura Yoshinori, Yamashita Makiko, Fang Shengguo, Tamura Takashi, Matsumoto Shin-Ei, Aiba Yoshihiro, Teruya Kiichiro, Osada Kazuhiro, Nishikawa Ryuhei, Shirahata Sanetaka
Department of Genetic Resources Technology, Faculty of Agriculture, Kyushu University, Fukuoka, Japan.
Biosci Biotechnol Biochem. 2004 Nov;68(11):2279-84. doi: 10.1271/bbb.68.2279.
An in vitro immunization (IVI) protocol enables antigen specific antibody production from L-Leucyl-L-Leucine methyl ester (LLME)-treated human peripheral blood lymphocytes (PBL) upon antigen stimulation in the presence of IL-2, IL-4, and muramyl dipeptide. In the course of our studies, we have found that IL-10 added at the antigen sensitization significantly augmented antibody production level from the LLME-treated PBL. In the present study, we tried to demonstrate the role of IL-10 in the augmentation of antibody production in an IVI protocol by clarifying the cytokine expression profiles in CD4(+) and CD8(+) T cells. The results showed that IL-10 skewed the Th1/Th2 balance to Th2-type responses by suppressing Th1-type cytokine production and augmenting Th2-type cytokine production in CD4(+) and CD8(+) T cells, as well as in CD19(+) B cells. Furthermore, IL-10 augmented the expression of CD38, an antigen marker of plasma cells, on B cells, which clearly indicates that IL-10 promoted differentiation and maturation of B cells in an IVI protocol. These results indicate that IL-10 plays an important role in setting the cellular milieu to produce antibodies in an IVI protocol.
一种体外免疫(IVI)方案能够在白细胞介素-2(IL-2)、白细胞介素-4(IL-4)和胞壁酰二肽存在的情况下,使经L-亮氨酰-L-亮氨酸甲酯(LLME)处理的人外周血淋巴细胞(PBL)在抗原刺激下产生抗原特异性抗体。在我们的研究过程中,我们发现,在抗原致敏时添加白细胞介素-10(IL-10)可显著提高经LLME处理的PBL的抗体产生水平。在本研究中,我们试图通过阐明CD4(+)和CD8(+) T细胞中的细胞因子表达谱,来证明IL-10在IVI方案中增强抗体产生的作用。结果表明,IL-10通过抑制CD4(+)和CD8(+) T细胞以及CD19(+) B细胞中Th1型细胞因子的产生并增强Th2型细胞因子的产生,使Th1/Th2平衡向Th2型反应倾斜。此外,IL-10增强了B细胞上浆细胞抗原标志物CD38的表达,这清楚地表明IL-10在IVI方案中促进了B细胞的分化和成熟。这些结果表明,IL-10在IVI方案中建立产生抗体的细胞环境方面发挥着重要作用。