摘要
目的 探讨再生障碍性贫血 (再障 )患者Th1、Th2细胞的数量、比例、产生细胞因子的功能状态及其与造血衰竭的关系 ,判断Th1细胞在重型再障 (SAA)发病机制中的作用。方法 ①采用甲基纤维素培养法扩增 11例SAA患者骨髓单个核细胞 (BMMNC)去除CD4+ 细胞前、后红系集落形成单位 (CFU E)、红系爆式集落形成单位 (BFU E)、粒 巨噬系集落形成单位 (CFU GM) ;②用流式细胞术检测经体外刺激后的 2 1例SAA患者及 17名正常人外周血单个核细胞 (PBMNC)中Th1、Th2细胞 ;③RT PCR检测 2 7例再障、2 6例非再障患者及 11名正常人未经体外刺激的BMMNC中Th1细胞的代表性细胞因子IFN γ和Th2细胞的代表性细胞因子IL 4的基因表达。结果 ①去除CD4+ 细胞后 ,SAA患者BMM NC中的CFU GM、CFU E和BFU E产率都有显著提高 ;②SAA患者外周血Th1与Th2细胞比例明显失衡 ,Th1细胞显著增多 ;③SAA和慢性再障患者骨髓中Th1细胞产生IFN γ的功能异常增高 ,而Th2细胞产生IL 4的功能未发现明显异常。结论 再障患者的CD4+ T淋巴细胞亚群失衡、Th1细胞数量增多及功能亢进可能是导致SAA骨髓衰竭的重要环节 ,也是再障区别于其它全血细胞减少症的标志之一。
Objective To detect the quantity, proportion and function of producing cytokines of Th1 and Th2 cells in aplastic anemia (AA) patients and their contribution to the hematopoietic failure. Methods ①Eleven patients with severe aplastic anemia(SAA) at diagnosis were observed by Marsh's method for the CFU E, BFU E and CFU GM before and after depletion of CD 4 + T lymphocytes from bone marrow mononuclear cells (BMMNC); ②Th1(CD 4 +IFN γ +) and Th2 (CD 4 +IL 4 +) cells in peripheral blood mononuclear cells (PBMNC) of 21 SAA patients and 17 normal controls were counted by FACS. ③mRNA expression of IFN γ and IL 4 gene in unstimulated BMMNC from 16 SAA patients, 11 chronic aplastic anemia(CAA) patients,26 other hematological diseases patients and 11 normal controls were measured by reverse transcriptase polymerase chain reaction (RT PCR). Result ①CFU E,CFU GM and BFU E increased significantly after depletion of CD 4 + T lymphocytes from BMMNC of SAA patients. ②The percentage of IFN γ producing CD 4 + T cell (Th1) of SAA patients was significantly higher than that of controls, the percentages of IL 4 producing CD 4 + T cells (Th2) had no difference between SAA patients and normal controls. ③IFN γ mRNA was detected in unstimulated BMMNC in 13 of 16 SAA patients, 6 of 11 CAA patients and one of 6 paroxysmal nocturnal hemoglobinuria (PNH) patients. The IFN γ mRNA was not detected in unstimulated BMMNC of 11 normal controls and other hematological diseases patients. Conclusions Disbalance of CD 4 + T lymphocytes subsets and increases in quantity and IFN γ producing function of Th1 cells might be important for the development of bone marrow failure in AA and in distinguishing AA from other kinds of pancytopenic diseases.
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2002年第11期574-577,共4页
Chinese Journal of Hematology
基金
天津市自然科学基金资助项目 (0 0 3 60 611)