再生障碍性贫血患者骨髓及外周血T、NK细胞膜分子和可溶性分子动态变化

T cell activation in patients with aplastic anemia

目的 研究T淋巴细胞及免疫分子在再生障碍性贫血 (AA)致病中的作用及其与临床疗效的相关性。方法 应用免疫荧光染色技术和流式细胞仪分析AA骨髓及外周血T淋巴细胞表型 ,ELISA测定骨髓和外周血白介素 2及其可溶性受体 (IL 2 ,sIL 2R)、可溶性Fas配体 (sFas L)和Flt3配体(FL)的水平。结果 (1)AA病人骨髓和外周血CD8+细胞百分率增加 ,CD4/CD8比例下降 ;骨髓血CD2 5 +和HLA DR+细胞百分率增多 ,急性AA增加尤为显著 (P <0 .0 1) ;骨髓血中CD16 +或CD5 6 +细胞百分率也明显增多 (P <0 .0 5 )。 (2 )所有AA患者骨髓及外周血IL 2含量均显著升高 ,绝大部分患者的sFas L含量增加 ,FL水平升高尤为显著 ,高达正常水平的 2 0倍。IL 2、sFas L和FL的含量与临床疗效密切相关 ,经治疗有效的患者骨髓和外周血的IL 2、sFas L和FL水平明显下降 ,但FL仍不能降至正常水平。结论 T细胞的异常活化 ,多种免疫分子表达的异常升高 ,以及产生针对自身造血干 /祖细胞的细胞毒效应 。

Objective To investigate the role of malfunctioning immune system in the pathogenesis of aplastic anemia(AA) and its relationship to clinical outcome. Methods Using flow cytometry and enzyme linked immunoadsorbent assay(ELISA), lymphocyte phenotypes and interleukin 2 and its receptor(IL 2, IL 2R) were studied with soluble Fas ligand(sFasL) and Flt3 ligand(FL) from bone marrow and peripheral blood of 21 patients with AA. Results 1. The percentage of CD8 + T cells increased and the ratio of CD4/CD8 decreased in patients with AA. Percentage of CD25 + and HLA DR + cells increased significantly in bone marrow of patients, especially in those with severe AA ( P <0.01). Bone marrow CD16 + and CD56 + cells increased significantly ( P <0.05). 2. The level of IL 2 was elevated both in peripheral blood and bone marrow and was associated with high level of soluble Fas ligand. The level of FL was about 20 times as high as that in controls. The levels of IL 2, sFasL and FL in patients′ bone marrow and peripheral blood were directly related to the clinical outcome and the levels of these cytokines decreased after effective treatment, but the level of FL did not return to normal. Conclusion Our studies indicated that an abnormally activated autoreaction of T lymphocytes, combined with several abnormally elevated, related immunologically active molecules which were cytotoxic for hematopoietic stem cells, founctioned as a major cause of hemopoietic failure in patients with AA.