Edinger Matthias, Hoffmann Petra, Ermann Joerg, Drago Kathryn, Fathman C Garrison, Strober Samuel, Negrin Robert S
Division of Bone Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, USA.
Nat Med. 2003 Sep;9(9):1144-50. doi: 10.1038/nm915. Epub 2003 Aug 17.
Mature donor T cells cause graft-versus-host disease (GVHD), but they are also the main mediators of the beneficial graft-versus-tumor (GVT) activity of allogeneic bone marrow transplantation. Suppression of GVHD with maintenance of GVT activity is a desirable outcome for clinical transplantation. We have previously shown that donor-derived CD4+CD25+ regulatory T cells inhibit lethal GVHD after allogeneic bone marrow transplantation across major histocompatibility complex (MHC) class I and II barriers in mice. Here we demonstrate that in host mice with leukemia and lymphoma, CD4+CD25+ regulatory T cells suppress the early expansion of alloreactive donor T cells, their interleukin-2-receptor (IL-2R) alpha-chain expression and their capacity to induce GVHD without abrogating their GVT effector function, mediated primarily by the perforin lysis pathway. Thus, CD4+CD25+ T cells are potent regulatory cells that can separate GVHD from GVT activity mediated by conventional donor T cells.
成熟的供体T细胞会引发移植物抗宿主病（GVHD），但它们也是异基因骨髓移植有益的移植物抗肿瘤（GVT）活性的主要介导者。在维持GVT活性的同时抑制GVHD是临床移植所期望的结果。我们之前已经表明，供体来源的CD4+CD25+调节性T细胞在小鼠体内跨越主要组织相容性复合体（MHC）I类和II类屏障进行异基因骨髓移植后，可抑制致死性GVHD。在此我们证明，在患有白血病和淋巴瘤的宿主小鼠中，CD4+CD25+调节性T细胞可抑制同种异体反应性供体T细胞的早期扩增、它们的白细胞介素-2受体（IL-2R）α链表达以及它们诱导GVHD的能力，而不会消除其主要由穿孔素裂解途径介导的GVT效应功能。因此，CD4+CD25+ T细胞是强大的调节性细胞，能够将GVHD与传统供体T细胞介导的GVT活性区分开来。
