Organ-derived dendritic cells have differential effects on alloreactive T cells
Organ-derived dendritic cells have differential effects on alloreactive T cells
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DOI：
10.1182/blood-2007-06-096602
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发表时间：
2008-03-01
期刊：
影响因子：
20.3
通讯作者：
van den Brink, Marcel R. M.
中科院分区：
文献类型：
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作者：
Kim, Theo D.;Terwey, Theis H.;van den Brink, Marcel R. M.
树突状细胞(DC)被认为是骨髓移植(BMT)后移植物抗宿主病(GVHD)的重要诱因。除了其启动功能外，树突状细胞还被证明通过诱导T细胞上特定的归巢分子来诱导器官趋化。利用CFSE标记细胞的过继转移，我们首次证明了同种异体反应性T细胞在体内差异地上调特定的归巢分子。来自GVHD靶器官肝和脾或皮肤和肠道引流淋巴结的宿主类型树突状细胞在体外有效地激活了原始同种异体T细胞，但肝脏来源的树突状细胞表现出较弱的刺激能力。在MHC不匹配的小鼠骨髓移植模型中，肠道来源的树突状细胞诱导具有肠道归巢表型的同种异体反应性供者T细胞，与来自脾、肝和外周淋巴结的树突状细胞刺激的T细胞相比，导致GVHD死亡率和发病率增加。然而，体内分析表明，归巢分子在体外对同种异体反应性T细胞的印迹只是暂时的。综上所述，器官来源的树突状细胞可以有效地诱导同种异体反应性T细胞上的特异性归巢分子。肠道归巢表型与小鼠骨髓移植后GVHD死亡率和发病率的增加相关，强调了肠道在GVHD病理生理学中的重要性。
Dendritic cells (DCs) are considered critical for the induction of graft-versus-host disease (GVHD) after bone marrow transplantation (BMT). In addition to their priming function, dendritic cells have been shown to induce organ-tropism through induction of specific homing molecules on T cells. Using adoptive transfer of CFSE-labeled cells, we first demonstrated that alloreactive T cells differentially up-regulate specific homing molecules in vivo. Host-type dendritic cells from the GVHD target organs liver and spleen or skin- and gut-draining lymph nodes effectively primed naive allogeneic T cells in vitro with the exception of liver-derived dendritic cells, which showed less stimulatory capacity. Gut-derived dendritic cells induced alloreactive donor T cells with a gut-homing phenotype that caused increased GVHD mortality and morbidity compared with T cells stimulated with dendritic cells from spleen, liver, and peripheral lymph nodes in an MHC-mismatched murine BMT model. However, in vivo analysis demonstrated that the in vitro imprinting of homing molecules on alloreactive T cells was only transient. In conclusion, organ-derived dendritic cells can efficiently induce specific homing molecules on alloreactive T cells. A gut-homing phenotype correlates with increased GVHD mortality and morbidity after murine BMT, underlining the importance of the gut in the pathophysiology of GVHD.