免疫活性细胞表达杀伤细胞抑制性受体与造血干细胞移植后移植物抗宿主病的关系

本研究的目的是探讨造血干细胞移植后杀伤细胞抑制性受体(KIR)CD158和CD94与GVHD发生的关系。用流式细胞术检测分析T淋巴细胞和NK细胞表达CD158a，CD158b和CD94表达状况，同时用PCR方法分析供受HLA—Cw配型，比较异基因外周血造血干细胞移植(allb-PBSCT)和脐血移植(UCBT)后该KIR分子变化和HLA—Cw相合或错配与GVHD发生的关系。结果表明：无论是PBSCT或是UCBT，移植后CD3^ CD158a^ 和CD3^ CD158b^ T细胞均增高并以CD8^ CD158b^ 细胞升高为主。发生急性与慢性GVHD组CD3^ CD158b^ 细胞均呈不同程度升高，在急性GVHD病例中升高最明显。急性GVHD期(即移植早期)KIR表达增高，慢性GVHD阶段(即移植后期)KIR呈减低趋势。CD94主要表达于CD3^ CD8^ T细胞，在UCBT或PBSCT后CD94在CD4^ T细胞和CD8^ T细胞均明显增高。5例HLA—Cw相合无1例发生重症GVHD；2例HLA—Cw不相合病例，有1例发生急重症GVHD，并死于间质性肺炎(IP)，另1例为AML(M5)，完全植入，无重度GVHD发生，但于53天后复发。4例相关相合移植中2例无急性GVHD，而无关相合4例均发生不同程度GVHD。结论：GVHD的发生与KIR表达有一定关系。CD158b分子可能是移植后早期T淋巴细胞活化的负调控分子。从T细胞表达KIR来理解GVHD发生机理，特别是与HLA-Cw特异性识别结合将有利于寻找一条新的特异性建立免疫耐受和减低GVHD的新策略。

Expression of Killer Cell Inhibitor Receptors on Immunocompetent Cells with Relation to Graft-versus-Host Disease after Hematopoietic Stem Cell Transplantation

The study was aimed at the exploration of relationship between T cells expressing killer cell inhibitor receptors (KIR, CD158 and CD94) and graft versus host disease (GVHD) after hematopoietic stem cell transplantation. The expression rates of CD158a, CD158b and CD94 on T cells and NK cell were detected by flow cytometry and donor/recipient HLA Cw was analyzed using PCR after peripheral blood stem cell transplantation (PBSCT) and umbilical cord blood transplantation (UCBT). After both PBSCT and UCBT, the rates of CD3 +CD158a + and CD3 +CD158b + T cells increased, especially the rate of CD8 +CD158b + T cells. In both acute and chronic GVHD groups, the rate of CD3 +CD158b + T cells increased, especially in acute GVHD. The CD94 mainly expressed on CD3 +CD8 +T cells. The percen tage of the expression of CD94 on CD4 + and CD8 + cells after UCBT and PBSCT increased significantly. The expression of KIR in GVHD (early stage of transplantation) increased but the expression of KIR in chronic GVHD (advanced stage of transplantation) decreased. Five patients who HLA Cw matched had no severe GVHD. In four patients who underwent allo PBSCT and UCBT from related HLA matched donors, only 2 patients had no aGVHD. Four patients underwent transplantation from unrelated HLA matched donors had GVHD. These observations suggested that there is some relationship between GVHD and KIR expression on T cells. CD158b might be an inhibitory molecule of T cell activated at early stage after transplantation. Understanding the mechanism of GVHD with the expression of KIR on T cells, especially those binding the HLA Cw might shed light on the establishment of the specific immunotolerance for the prevention of GVHD. To pay attention to HLA Cw typing is very important to reduce GVHD and increase GVL effect in related or unrelated HLA matched transplantation.