Donor-type CD4(+)CD25(+) regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation.
Donor-type CD4(+)CD25(+) regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation.
复制标题
供体型CD4（+）CD25（+）调节性T细胞在同种异体骨髓移植后抑制致命的急性移植物抗宿主疾病。
DOI：
10.1084/jem.20020399
复制
发表时间：
2002-08-05
影响因子：
15.3
通讯作者：
Strober, Samuel
中科院分区：
文献类型：
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作者：
Hoffmann, Petra;Ermann, Joerg;Edinger, Matthias;Fathman, C Garrison;Strober, Samuel
急性移植物抗宿主病（Acute graft-versus-host disease，aGVHD）仍是临床异基因骨髓移植的主要障碍。CD 4 + CD 25+调节性T（Treg）细胞最近被证明在体外抑制CD 4 + CD 25 − T细胞对同种异体抗原刺激的增殖反应，并且是供体T细胞的离体耐受所必需的，这导致其诱导aGVHD的潜力降低。在这里，我们表明，从未耐受的供体C57 BL/6（H-2b）小鼠的脾脏或骨髓中分离的CD 4 + CD 25 + T细胞仍然是体外同种异体反应和体内照射BALB/c（H-2d）宿主中C57 BL/6 CD 4 + CD 25 − T细胞诱导的致死性aGVHD的有效抑制剂。以1：1的比例添加CD 4 + CD 25 + Treg细胞与应答/诱导CD 4 + CD 25 − T细胞导致对混合白细胞反应的>90%抑制和对致死性GVHD的显著保护。这种保护作用部分取决于转移的CD 4 + CD 25 + T细胞分泌白细胞介素10的能力，并且如果Treg细胞是供体来源而不是宿主来源，则会发生这种保护作用。我们的研究结果表明，供体型CD 4 + CD 25 + Treg和常规CD 4 + CD 25 − T细胞的平衡可以决定aGVHD的结局。
Acute graft-versus-host disease (aGVHD) is still a major obstacle in clinical allogeneic bone marrow (BM) transplantation. CD4+CD25+ regulatory T (Treg) cells have recently been shown to suppress proliferative responses of CD4+CD25− T cells to alloantigenic stimulation in vitro and are required for ex vivo tolerization of donor T cells, which results in their reduced potential to induce aGVHD. Here we show that CD4+CD25+ T cells isolated from the spleen or BM of donor C57BL/6 (H-2b) mice that have not been tolerized are still potent inhibitors of the alloresponse in vitro and of lethal aGVHD induced by C57BL/6 CD4+CD25− T cells in irradiated BALB/c (H-2d) hosts in vivo. The addition of the CD4+CD25+ Treg cells at a 1:1 ratio with responder/inducer CD4+CD25− T cells resulted in a >90% inhibition of the mixed leukocyte reaction and marked protection from lethal GVHD. This protective effect depended in part on the ability of the transferred CD4+CD25+ T cells to secrete interleukin 10 and occurred if the Treg cells were of donor, but not host, origin. Our results demonstrate that the balance of donor-type CD4+CD25+ Treg and conventional CD4+CD25− T cells can determine the outcome of aGVHD.