Depletion of host CCR7(+) dendritic cells prevented donor T cell tissue tropism in anti-CD3-conditioned recipients.
Depletion of host CCR7(+) dendritic cells prevented donor T cell tissue tropism in anti-CD3-conditioned recipients.
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DOI：
10.1016/j.bbmt.2014.03.029
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发表时间：
2014-07
影响因子：
4.3
通讯作者：
Zeng, Defu
中科院分区：
文献类型：
--
作者：
He, Wei;Racine, Jeremy J.;Johnston, Heather F.;Li, Xiaofan;Li, Nainong;Cassady, Kaniel;Liu, Can;Deng, Ruishu;Martin, Paul;Forman, Stephen;Zeng, Defu
我们之前报道过，HCT 前的抗 CD3 mAb 治疗可预防小鼠移植物抗宿主病 (GVHD) 并保留移植物抗白血病 (GVL) 效应。这些效应与组织特异性归巢和趋化因子受体的供体 T 细胞表达下调、供体 T 细胞向 GVHD 靶组织迁移的显着减少以及肠系膜淋巴结 (MLN) 中 CD103+ 树突状细胞 (DC) 的缺失有关。 MLN CD103+ DCs and peripheral lymph node (PLN) DCs include CCR7+ and CCR7− subsets, but the role of these DC subsets in regulating donor T cell expression of homing and chemokine receptors remain unclear.在这里，我们发现 MLN 中的受体 CCR7+ DC（而非 CCR7− DC）以视黄酸 (RA) 依赖性方式诱导供体 T 细胞表达肠道特异性归巢和趋化因子受体。 CCR7 regulated activated DC migration from tissue to draining lymph node, but was not required for the ability of DCs to induce donor T cell expression of tissue-specific homing and chemokine receptors.最后，抗CD3治疗通过诱导MLN和PLN中CCR7+ DC的连续扩增和凋亡来耗尽CCR7+而不是CCR7− DC。 CCR7+ DC 的凋亡与 DC 的 Fas 表达和 NK 细胞的上调相关，但与淋巴结中的 T、B 或树突状细胞的 FasL 表达的上调无关。这些结果表明，消除 CCR7+ 宿主型 DC，随后抑制供体 T 细胞迁移至 GVHD 靶组织，可能是预防急性 GVHD 和保留 GVL 效应的有效方法 (244)。
We reported previously that anti-CD3 mAb treatment before HCT prevented graft versus host disease (GVHD) and preserved graft-versus-leukemia (GVL) effects in mice. These effects were associated with down-regulated donor T cell expression of tissue-specific homing and chemokine receptors, marked reduction of donor T cell migration into GVHD target tissues, and deletion of CD103+ dendritic cells (DCs) in mesenteric lymph nodes (MLN). MLN CD103+ DCs and peripheral lymph node (PLN) DCs include CCR7+ and CCR7− subsets, but the role of these DC subsets in regulating donor T cell expression of homing and chemokine receptors remain unclear. Here, we show that recipient CCR7+ but not CCR7− DCs in MLN induced donor T cell expression of gut-specific homing and chemokine receptors in a retinoid acid (RA)-dependent manner. CCR7 regulated activated DC migration from tissue to draining lymph node, but was not required for the ability of DCs to induce donor T cell expression of tissue-specific homing and chemokine receptors. Finally, anti-CD3 treatment depleted CCR7+ but not CCR7− DCs by inducing sequential expansion and apoptosis of CCR7+ DCs in MLN and PLN. Apoptosis of CCR7+ DCs was associated with DC up-regulation of Fas expression and NK cell but not T, B or dendritic cell upregulation of FasL expression in the lymph nodes. These results suggest that depletion of CCR7+ host-type DCs with subsequent inhibition of donor T cell migration into GVHD target tissues can be an effective approach in prevention of acute GVHD and preservation of GVL effects (244).
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DOI：
10.1084/jem.20060376
发表时间：
2006-08-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
20.3
作者：
Kim, Theo D.;Terwey, Theis H.;van den Brink, Marcel R. M.
通讯作者：
van den Brink, Marcel R. M.
影响因子：
20.3
作者：
Beilhack, A;Schulz, S;Negrin, RS
通讯作者：
Negrin, RS
影响因子：
4.3
作者：
Carpenter, PA;Lowder, J;Anasetti, C
通讯作者：
Anasetti, C
影响因子：
5
作者：
Limana, Federica;Bertolami, Chiara;Capogrossi, Maurizio C.
通讯作者：
Capogrossi, Maurizio C.