Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
Cell Mol Immunol. 2010 Jan;7(1):44-50. doi: 10.1038/cmi.2009.103.
CD4(+) regulatory T cells (Tregs) play an important role in maintaining immune tolerance by suppressing pathologic immune responses. The generation of large numbers of antigen-specific Tregs ex vivo is critical for the development of clinical immunotherapy based on the adoptive transfer of Tregs. Both CD40-activated B cells (CD40-B) and immature dendritic cells (imDCs) have been used as professional antigen-presenting cells (APCs) to generate antigen-specific Tregs. However, the efficiencies of CD40-B and imDCs to generate CD4(+) Tregs have not been compared directly and the mechanism driving the generation of these Tregs remains largely unknown. In this study, we found that CD40-B exhibited mature phenotypes and were more able to induce and expand CD4(high)CD25(+) Tregs than imDCs. Moreover, Tregs induced by CD40-B had greater suppressive capacity than those induced by imDCs. The generation of CD4(high)CD25(+) Tregs by CD40-B and imDCs is cell-cell contact dependent and partially relies on the expression of human leukocyte antigen (HLA)-DR and CD80/86. Differences in CD4(high)CD25(+) Treg generation efficiency were largely explained by the production of endogenous IL-2 by CD40-B. Our results suggest that CD40-B is better able to generate large numbers of antigen-specific Tregs than imDCs. Additionally, using CD40-B to generate Tregs may accelerate the clinical use of Treg-based immunotherapy in the treatment of allograft rejection, graft versus host disease (GVHD) and autoimmune diseases.
CD4(+) 调节性 T 细胞 (Tregs) 通过抑制病理性免疫反应在维持免疫耐受方面发挥着重要作用。大量体外产生的抗原特异性 Tregs 对于基于 Tregs 过继转移的临床免疫治疗的发展至关重要。CD40 激活的 B 细胞 (CD40-B) 和未成熟树突状细胞 (imDCs) 已被用作专业抗原提呈细胞 (APCs) 来产生抗原特异性 Tregs。然而，CD40-B 和 imDCs 产生 CD4(+) Tregs 的效率尚未直接比较，驱动这些 Tregs 产生的机制在很大程度上仍不清楚。在这项研究中，我们发现 CD40-B 表现出成熟表型，并且比 imDCs 更能够诱导和扩增 CD4(high)CD25(+) Tregs。此外，CD40-B 诱导的 Tregs 比 imDCs 诱导的 Tregs 具有更强的抑制能力。CD40-B 和 imDCs 产生 CD4(high)CD25(+) Tregs 依赖细胞-细胞接触，部分依赖于人类白细胞抗原 (HLA)-DR 和 CD80/86 的表达。CD4(high)CD25(+) Treg 生成效率的差异在很大程度上可以通过 CD40-B 产生内源性 IL-2 来解释。我们的结果表明，CD40-B 比 imDCs 更能产生大量的抗原特异性 Tregs。此外，使用 CD40-B 产生 Tregs 可能会加速基于 Treg 的免疫治疗在同种异体移植排斥、移植物抗宿主病 (GVHD) 和自身免疫性疾病治疗中的临床应用。
