National School of Biological Sciences, Instituto Politécnico Nacional, México City, México.
Stem Cells Dev. 2010 Mar;19(3):333-40. doi: 10.1089/scd.2009.0216.
Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for some hematological diseases; however, graft-versus-host disease (GVHD) is still one of the most important and deleterious complications. Regulatory T cells and iNKT cells can decrease the incidence and severity of GVHD, while preserving the graft-versus-tumor response. In order to analyze the relationship between the transfused dose of these cells, the presence of GVHD and survival, 15 normal donors and 15 patients with hematological diseases who underwent allogeneic HSCT from HLA-identical siblings were studied. The mobilization and infused doses of valpha24-vbeta11(iNKT cells) lymphocytes and CD4+CD25+FoxP3+, CD4+CD25+FoxP3+CD62L+, regulatory T cells were analyzed. All patients were conditioned with busulfan and cyclophosphamide and received cyclosporine and methotrexate as GVHD prophylaxis. iNKT and FoxP3 cells were mobilized after G-CSF administration. Acute GVHD was present in 9 of 15 (60%) and cGVHD in 7 of 13 (54%) patients. Patients who received a dose <0.6 x 10(6)/kg of iNKT cells and >4 x 10(6)/kg of FoxP3 had better disease-free survival and overall survival. Individuals transfused with >1.1 x 10(6)/kg of FoxP3+ CD62L+ Treg cells had better overall survival. In conclusion, iNKT and Treg cells are mobilized with G-CSF in healthy donors and the dose of iNKT cells and FoxP3 and CD62L+ regulatory T cells is of clinical importance in human HSCT.
同种异体造血干细胞移植（HSCT）是治疗某些血液疾病的首选方法；然而，移植物抗宿主病（GVHD）仍然是最重要和最具危害性的并发症之一。调节性 T 细胞和 iNKT 细胞可以降低 GVHD 的发生率和严重程度，同时保留移植物抗肿瘤反应。为了分析这些细胞的输注剂量、GVHD 的存在与存活率之间的关系，对 15 名正常供体和 15 名接受 HLA 相同同胞异体 HSCT 的血液系统疾病患者进行了研究。分析了 valpha24-vbeta11(iNKT 细胞)淋巴细胞和 CD4+CD25+FoxP3+、CD4+CD25+FoxP3+CD62L+、调节性 T 细胞的动员和输注剂量。所有患者均采用白消安和环磷酰胺预处理，并接受环孢素和甲氨蝶呤预防 GVHD。iNKT 和 FoxP3 细胞在 G-CSF 给药后动员。15 例患者中有 9 例（60%）出现急性 GVHD，13 例中有 7 例（54%）出现慢性 GVHD。接受剂量＜0.6×10(6)/kg iNKT 细胞和＞4×10(6)/kg FoxP3 的患者无病生存率和总生存率更好。输注＞1.1×10(6)/kg FoxP3+CD62L+Treg 细胞的个体总生存率更好。总之，健康供体可通过 G-CSF 动员 iNKT 和 Treg 细胞，iNKT 细胞、FoxP3 和 CD62L+调节性 T 细胞的剂量在人类 HSCT 中具有临床意义。
