Regulatory dendritic cells protect against cutaneous chronic graft-versus-host disease mediated through CD4+CD25+Foxp3+ regulatory T cells
Regulatory dendritic cells protect against cutaneous chronic graft-versus-host disease mediated through CD4+CD25+Foxp3+ regulatory T cells
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DOI：
10.1182/blood-2007-04-086470
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发表时间：
2007-11-15
期刊：
影响因子：
20.3
通讯作者：
Sato, Katsuaki
中科院分区：
文献类型：
--
作者：
Fujita, Shigeharu;Sato, Yumiko;Sato, Katsuaki
慢性移植物抗宿主病（cGVHD）是异基因骨髓移植（alloBMT）中发病和死亡的常见原因。然而，治疗cGVHD的有效策略尚未建立。在这项研究中，我们检查了修饰的树突状细胞（DC）的治疗效用，其调节免疫应答的能力比先前已知的致耐受性DC、主要组织相容性复合物相容性中的调节性DC（DC）更大，和同种异体BMT中cGVHD的多个次要组织相容性抗原不相容性模型在用受体进行同种异体BMT后受体小鼠的治疗-与雷帕霉素相比，DC-DC对皮肤cGVHD的发生率和严重程度的抑制作用更大，而用顺从型成熟DC治疗则促进了发病机制。对受体小鼠的分析表明，致敏型DC的保护作用涉及从供体来源的CD 4（+）CD 25（-）Foxp 3（-）T细胞外周产生同种异体反应性CD 4（+）CD 25（+）Foxp 3（+）调节性T（T-R）细胞。因此，使用DC的免疫疗法是通过诱导涉及CD 4（+）CD 25（+）Foxp 3（+）TR细胞的显性耐受来介导的用于治疗alloBMT中的cGVHD的有希望的策略。
Chronic graft-versus-host disease (cGVHD) is a common cause of morbidity and mortality in allogeneic bone marrow transplantation (alloBMT). However, effective strategies for the treatment of cGVHD have not been established. In this study, we examined the therapeutic utility of modified dendritic cells (DCs) with a greater capacity to regulate immune responses than previously known tolerogenic DCs, regulatory DCs (DCregs) in the major histocompatibility complex-compatible, and multiple minor histocompatibility antigen-incompatible model of cGVHD in alloBMT Treatment of the recipient mice after alloBMT with the recipient-type DCregs led to greater suppression of the incidence and severity of cutaneous cGVHD than rapamycin, whereas treatment with the recipient-type mature DCs promoted the pathogenesis. Analysis of the recipient mice suggested that the protective effect of the recipient-type DCregs involved the peripheral generation of alloreactive CD4(+)CD25(+)Foxp3(+)regulatory T (T-R) cells from donor-derived CD4(+)CD25(-)Foxp3(-)T cells. Thus, immunotherapy with DCregs is a promising strategy for the treatment of cGVHD in alloBMT mediated through the induction of a dominant tolerance involving CD4(+)CD25(+)Foxp3(+) TR cells.