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。
Objective To explore the influence factors of reconstitution of killer cell immunoglobulin-hke 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. Rebulls 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.