体外不去T细胞单倍体造血干细胞移植后NK细胞免疫球蛋白样受体重建的影响因素

目的探讨造血干细胞移植（HSCT）后早期NK细胞免疫球蛋白样受体（KIR）恢复的影响因素。方法借助三色和四色荧光标记技术，用流式细胞术对24例行体外不去T细胞的HLA不相合HSCT的患者（移植前、＋30天、＋60天）及其供者外周血中NK细胞KIR的表达进行了测定，包括CD158a（KIR2DL1）、CD158b（KIR2DL2）和CD158e（KIR3DL1）；同时用流式细胞术对移植物中CD3、CD4、CD8、CD14、CD34的含量进行了测定。结果发生Ⅱ～Ⅳ度急性移植物抗宿主病（aGVHD）患者在＋30天NK细胞KIR的表达明显低于0～I度aGVHD患者，CD158b分别为（19．27±9．40）％和（28．92±10．59）％，P=0．018]和CD158aCD158b分别为（7．30±4．73）％和（14．26±9．71）％，P=0．016]尤为显著。多因素分析表明移植物中CD4^＋T细胞是引起aGVHD的危险因素。进一步的相关分析表明每千克体重输入的CD4^＋T细胞数与移植后早期NK细胞上CD158a、CD158aCD158b和CD158e的表达呈明显的负相关。结论体外不去T细胞的HLA不相合的HSCT中，不仅移植后aGVHD的发生或其相应的治疗措施抑制了移植后早期NK细胞上KIR的恢复；而且移植物中T细胞也直接或间接影响了移植后早期NK细胞上KIR的重建，进而影响了NK细胞功能的恢复。

Influence factors of reconstitution of killer cell immunoglobulin-like receptor on NK cells following non-T-cell-depleted haploidentical hematopoietic stem cell transplantation

OBJECTIVE: To explore the influence factors of reconstitution of killer cell immunoglobulin-like receptor (KIR) on NK cells in the early stage after non-T cells depletion (non-TCD) HLA-mismatched hematopoitic stem cell transplantation (HSCT). METHODS: The expression of KIR (CD158a, CD158b, CD158e) on NK cells from peripheral blood (PB) in 24 patients and their donors before and after HLA-mismatched non-TCD HSCT on day +30, +60, were detected by flow cytometry (FCM). Meanwhile the number of the CD3, CD4, CD8, CD14, CD34 positive cells in the allograft were also tested by FCM. RESULTS: The high dose of CD4+ T cells in the allograft was positively correlated with increased aGVHD occurrence and inversely with the expression of CD158a, CD158aCD158b and CD158e on day +30 and +60. Furthermore, the expression of the CD158b (19.27 +/- 9.40)% vs (28.92 +/- 10.59)%, P = 0.018 ] and CD158aCD158b (7.30 +/- 4.73)% vs ( 14.26 +/- 9.71)%, P = 0.016] were higher in patients with 0 - I aGVHD than in patients with II - IV aGVHD. CONCLUSION: Both of the T cells in the allograft and the occurrence of GVHD in the early stage after transplantation delayed the recovery of KIR on NK cells.