In vivo-activated CD103+CD4+ regulatory T cells ameliorate ongoing chronic graft-versus-host disease
In vivo-activated CD103+CD4+ regulatory T cells ameliorate ongoing chronic graft-versus-host disease
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DOI：
10.1182/blood-2008-02-140277
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发表时间：
2008-09-01
期刊：
影响因子：
20.3
通讯作者：
Zeng, Defu
中科院分区：
文献类型：
--
作者：
Zhao, Dongchang;Zhang, Chunyan;Zeng, Defu
CD 103（α E β 7）已被证明是用于鉴定体内活化的FoxP 3（+）CD 4（+）调节性T（Treg）细胞的极好标志物。目前尚不清楚接受者体内激活的供体型CD 103（+）Treg细胞回输是否可以改善正在进行的慢性移植物抗宿主病（GVHD）。在这里，我们发现，在DBA/2（H-2（d））供体到BALB/c（H-2（d））受体的慢性GVHD模型中，来自受体的供体型CD 103（+）Treg细胞比来自供体的CD 25（hi）天然Treg细胞在逆转GVHD和组织损伤的临床体征方面更有效。此外，与CD 25（hi）天然Treg细胞相比，CD 103（+）Treg细胞表达高水平的CCR 5但低水平的CD 62 L，并直接迁移至GVHD靶组织。此外，CD 103（+）Treg细胞强烈抑制供体CD 4（+）T细胞增殖;它们还诱导体内活化的CD 4（+）T和B细胞凋亡，并显著减少GVHD靶组织中的致病性T和B细胞。这些结果表明，来自慢性GVHD受者的CD 103（+）Treg细胞是功能性的，并且CD 103（+）Treg细胞的再输注可以改变慢性GVHD受者中Treg细胞和致病性T细胞之间的平衡并改善正在进行的疾病。
CD103 (alpha E beta 7) has been shown to be an excellent marker for identifying in vivo-activated FoxP3(+)CD4(+) regulatory T (Treg) cells. It is unknown whether reinfusion of in vivo-activated donor-type CD103(+) Treg cells from recipient can ameliorate ongoing chronic graft-versus-host disease (GVHD). Here, we showed that, in a chronic GVHD model of DBA/2 (H-2(d)) donor to BALB/c (H-2(d)) recipient, donor-type CD103(+) Treg cells from recipients were much more potent than CD25(hi) natural Treg cells from donors in reversing clinical signs of GVHD and tissue damage. Furthermore, in contrast to CD25(hi) natural Treg cells, CD103(+) Treg cells expressed high levels of CCR5 but low levels of CD62L and directly migrated to GVHD target tissues. In addition, the CD103(+) Treg cells strongly suppressed donor CD4(+) T-cell proliferation; they also induced apoptosis of in vivo-activated CD4(+) T and B cells and significantly reduced pathogenic T and B cells in GVHD target tissues. These results indicate that CD103(+) Treg cells from chronic GVHD recipients are functional, and reinfusion of the CD103(+) Treg cells can shift the balance between Treg cells and pathogenic T cells in chronic GVHD recipients and ameliorate ongoing disease.