Department of Microbiology and Immunology, Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, PR China.
Cytokine. 2011 May;54(2):205-11. doi: 10.1016/j.cyto.2011.01.008. Epub 2011 Feb 5.
High mobility group box 1 protein (HMGB1) has been identified as a late proinflammatory cytokine and plays a key role in immune regulation. However, it is not yet clear whether HMGB1 can induce the activation and differentiation of dendritic cell (DC) subsets and subsequently modulate immune function of T cells. This study was performed to investigate the effect of HMGB1 on the differentiation of splenic DCs and its influence on T cell-mediated immunity in terms of DC subsets CD11c(low)CD45RB(high) DCs and CD11c(high)CD45RB(low) DCs in male BALB/c mice spleens in vitro.
MACS microbeads were used to isolate splenic DCs, CD11c(low)CD45RB(high) DCs, CD11c(high)CD45RB(low) DCs and CD4(+) T cells. The percentage of CD11c(low)CD45RB(high) DCs was significantly increased after treatment with HMGB1 compared to their counterparts (CD11c(high)CD45RB(low) DCs). It was found that unlike the gradually increasing interleukin (IL)-12 secretion of CD11c(high)CD45RB(low) DCs induced by HMGB1, CD11c(low)CD45RB(high) DCs showed a obvious dose-dependent response between IL-10 production and HMGB1 stimulation. In order to verify whether the alteration of CD4(+) T cells was mainly associated with the differentiation of splenic DCs mediated by HMGB1 to CD11c(low)CD45RB(high) DCs, anti-IL-12 receptor (IL-12R) or anti-IL-10R monoclonal antibody was used to inhibit the effect of CD11c(high)CD45RB(low) DCs or CD11c(low)CD45RB(high) DCs in CD4(+) T cells mixed lymphocyte reaction culture. After treatment with anti-IL-12R or anti-IL-10 monoclonal antibody in CD4(+) T cells+CD11c(high)CD45RB(low) DCs or CD11c(low)CD45RB(high) DCs mixed lymphocyte reaction, the induction of these DCs on T cells was inhibited dramatically.
These data demonstrated that HMGB1 might induce the differentiation of splenic DCs to CD11c(low)CD45RB(high) DCs followed by shifting of Th1 to Th2 with enhancement of T lymphocyte immune function in vitro. Also, the effect of HMGB1 on T cell differentiation to Th2 was not associated with the inhibition of IL-12 production in CD11c(high)CD45RB(low) DCs.
高迁移率族蛋白 B1（HMGB1）已被鉴定为晚期促炎细胞因子，在免疫调节中发挥关键作用。然而，目前尚不清楚 HMGB1 是否能诱导树突状细胞（DC）亚群的激活和分化，进而调节 T 细胞的免疫功能。本研究旨在探讨 HMGB1 对雄性 BALB/c 小鼠脾脏中 DC 亚群 CD11c（低）CD45RB（高）DC 和 CD11c（高）CD45RB（低）DC 体外分化的影响及其对 T 细胞介导的免疫功能的影响。
使用 MACS 微珠分离脾 DC、CD11c（低）CD45RB（高）DC、CD11c（高）CD45RB（低）DC 和 CD4（+）T 细胞。与对照组（CD11c（高）CD45RB（低）DC）相比，用 HMGB1 处理后 CD11c（低）CD45RB（高）DC 的比例明显增加。结果发现，与 HMGB1 诱导的 CD11c（高）CD45RB（低）DC 中 IL-12 分泌逐渐增加不同，CD11c（低）CD45RB（高）DC 表现出与 HMGB1 刺激之间呈明显的剂量依赖性 IL-10 产生反应。为了验证 CD4（+）T 细胞的改变是否主要与 HMGB1 介导的脾 DC 向 CD11c（低）CD45RB（高）DC 的分化有关，用抗 IL-12 受体（IL-12R）或抗 IL-10R 单克隆抗体抑制 CD4（+）T 细胞混合淋巴细胞反应培养中 CD11c（高）CD45RB（低）DC 或 CD11c（低）CD45RB（高）DC 的作用。在用抗 IL-12R 或抗 IL-10 单克隆抗体处理 CD4（+）T 细胞+CD11c（高）CD45RB（低）DC 或 CD11c（低）CD45RB（高）DC 混合淋巴细胞反应后，这些 DC 对 T 细胞的诱导作用明显受到抑制。
这些数据表明，HMGB1 可能诱导脾 DC 向 CD11c（低）CD45RB（高）DC 的分化，随后通过增强 T 淋巴细胞免疫功能向 Th2 转移，从而导致体外 Th1 向 Th2 的转移。此外，HMGB1 对 T 细胞向 Th2 分化的影响与抑制 CD11c（高）CD45RB（低）DC 中 IL-12 的产生无关。
