Background. Nonspecific immunosuppressive therapy for graft rejection and graft-versus-host disease (GVHD) is often accompanied by severe side effects such as opportunistic infections and cancers. Several approaches have been developed to suppress transplantation reactions using tolerogenic cells, including induction of FoxP3⁺ Tregs with antigen-loaded dendritic cells (DCs) and induction of CD4⁺IL-10⁺ cells with interleukin IL-10-producing DCs. Here, we assessed the effectiveness of both approaches in the suppression of graft rejection and GVHD. Methods. IL-10-producing DCs were generated by the transfection of DCs with DNA constructs encoding mouse IL-10. Antigen-loaded DCs from C57BL/6 mice were generated by transfection with DNA constructs encoding antigenic determinants from the H2 locus of CBA mice which differ from the homologous antigenic determinants of C57BL/6 mice. Results. We found that both IL-10-producing DCs and antigen-loaded immature DCs could suppress graft rejection and GVHD but through distinct nonspecific and antigen-specific mechanisms, respectively. Discussion. We provide data that the novel approach for DCs antigen loading using DNA constructs encoding distinct homologous determinants derived from major histocompatibility complex genes is effective in antigen-specific suppression of transplantation reactions. Such an approach eliminates the necessity of donor material use and may be useful in immunosuppressive therapy side effects prevention.

中文翻译：

---

用 CBA 小鼠的 MHC 抗原决定簇转染的树突细胞诱导 C57Bl/6 小鼠的抗原特异性耐受性。

背景。针对移植排斥和移植物抗宿主病 (GVHD) 的非特异性免疫抑制疗法通常伴随着严重的副作用，例如机会性感染和癌症。已经开发了几种使用致耐受性细胞抑制移植反应的方法，包括用载有抗原的树突细胞 (DC) 诱导FoxP3 ^{+ Tregs 和用产生白介素 IL-10 的 DCs 诱导 CD4 +} IL-10 ⁺细胞。在这里，我们评估了这两种方法在抑制移植排斥和 GVHD 方面的有效性。方法. 产生 IL-10 的 DC 是通过用编码小鼠 IL-10 的 DNA 构建体转染 DC 产生的。来自 C57BL/6 小鼠的载有抗原的 DCs 是通过转染编码来自 CBA 小鼠 H2 基因座的抗原决定簇的 DNA 构建体产生的，这些抗原决定簇不同于 C57BL/6 小鼠的同源抗原决定簇。结果。我们发现产生 IL-10 的 DCs 和负载抗原的未成熟 DCs 都可以抑制移植排斥和 GVHD，但分别通过不同的非特异性和抗原特异性机制。讨论. 我们提供的数据表明，使用编码源自主要组织相容性复合物基因的不同同源决定簇的 DNA 构建体加载 DCs 抗原的新方法在抗原特异性抑制移植反应中是有效的。这种方法消除了使用供体材料的必要性，并可用于预防免疫抑制治疗的副作用。