Extracorporeal photopheresis attenuates murine graft-versus-host disease via bone marrow-derived interleukin-10 and preserves responses to dendritic cell vaccination.
Extracorporeal photopheresis attenuates murine graft-versus-host disease via bone marrow-derived interleukin-10 and preserves responses to dendritic cell vaccination.
复制标题
DOI：
10.1016/j.bbmt.2010.12.712
复制
发表时间：
2011-06
影响因子：
4.3
通讯作者：
Fry, Terry J.
中科院分区：
文献类型：
--
作者：
Capitini, Christian M.;Davis, Jessica P. E.;Larabee, Shannon M.;Herby, Sarah;Nasholm, Nicole M.;Fry, Terry J.
体外光采术 (ECP) 正在成为移植物抗宿主病 (GVHD) 的一种治疗方法，但其完整的作用机制和对免疫的影响尚未完全确定。小鼠轻微组织相容性抗原不匹配骨髓移植 (alloBMT) 后，无论 ECP 处理的脾细胞的供体菌株如何，将 ECP 处理的脾细胞与充满 T 细胞的骨髓共输注都会减弱 GVHD，并且与调节性 T 细胞数量增加相关。骨髓树突状细胞 (mDC) 与 ECP 处理的脾细胞共培养，在脂多糖次最大刺激后，白细胞介素 (IL)-10 的产生增加。此外，当用作体内疫苗时，暴露于 ECP 处理的脾细胞的雄性 mDC 诱导 CD8+ HY 反应的能力较差。在 T 细胞耗尽的 alloBMT 后延迟供体淋巴细胞输注 (DLI) 之前施用 ECP 处理的脾细胞的功效得到增强，从而允许在没有胸腺的情况下施用足够数量的 T 细胞对 mDC 疫苗接种做出反应。最后，ECP 处理的脾细胞的治疗效果在 IL-10 缺乏的骨髓受者中消失。我们证明，无论 ECP 处理的细胞来源如何，ECP 处理的脾细胞都会通过一种可能涉及 DC 调节的机制来减弱 GVHD，并且需要骨髓来源细胞产生的 IL-10。重要的是，ECP 处理的脾细胞对 GVHD 的减弱允许在 alloBMT 后对 DC 疫苗产生 DLI 依赖性反应。
Extracorporeal photopheresis (ECP) is emerging as a therapy for graft-versus-host-disease (GVHD), but the full mechanism of action and the impact on immunity have not been fully established. After murine minor histocompatibility antigen-mismatched bone marrow transplant (alloBMT), co-infusion of ECP-treated splenocytes with T cell-replete bone marrow attenuated GVHD irrespective of the donor strain of the ECP-treated splenocytes, and was associated with increased numbers of regulatory T cells. Co-culture of myeloid dendritic cells (mDC) with ECP-treated splenocytes resulted in increased interleukin (IL)-10 production after sub-maximal stimulation with lipopolysaccharide. Furthermore, male mDCs exposed to ECP-treated splenocytes were less potent at inducing CD8+ HY-responses when used as a vaccine in vivo. The efficacy of ECP-treated splenocytes was enhanced when administered just prior to delayed donor lymphocyte infusion (DLI) following T cell depleted alloBMT, allowing for the administration of sufficient numbers of T cells to respond to mDC vaccination in the absence of a thymus. Finally, the therapeutic effect of ECP-treated splenocytes were lost in recipients of IL-10 deficient bone marrow. We demonstrate that ECP-treated splenocytes attenuate GVHD irrespective of the source of ECP-treated cells via a mechanism that likely involves modulation of DCs, and requires IL-10 produced by bone marrow-derived cells. Importantly, attenuation of GVHD by ECP-treated splenocytes permits DLI-dependent responses to DC vaccines following alloBMT.
登录
查看更多内容
影响因子：
6.2
作者：
Di Biaso, Iolanda;Di Maio, Lucia;Biagi, Ettore
通讯作者：
Biagi, Ettore
影响因子：
4.8
作者：
Shaughnessy PJ;Bolwell BJ;van Besien K;Mistrik M;Grigg A;Dodds A;Prince HM;Durrant S;Ilhan O;Parenti D;Gallo J;Foss F;Apperley J;Zhang MJ;Horowitz MM;Abhyankar S
通讯作者：
Abhyankar S
影响因子：
20.3
作者：
Flowers, Mary E. D.;Apperley, Jane F.;Greinix, Hildegard T.
通讯作者：
Greinix, Hildegard T.
影响因子：
7.2
作者：
Morelli, Adrian E.;Larregina, Adriana T.
通讯作者：
Larregina, Adriana T.
影响因子：
4.8
作者：
Messina, C.;Faraci, M.;Calore, E.
通讯作者：
Calore, E.