再生障碍性贫血患儿CD+4CD+25T细胞及TGF β1Flt 3L水平变化的意义

目的评价免疫调节T细胞和细胞因子在再生障碍性贫血(再障)细胞免疫功能紊乱中的作用。方法2004 02—2005 06中山大学第二附属医院采用流式细胞术检测27例特发性再障患儿骨髓及外周血淋巴细胞亚群和CD+4CD+25T细胞水平，ELISA检测骨髓转化生长因子(TGF β1)和Flt 3L水平，并与正常儿童对照。结果与对照组比较，初诊再障患儿外周血和骨髓CD+8T细胞均显著增高(P<0.05)，重型再障(SAA)组伴外周血CD-3CD+56NK细胞及骨髓B细胞显著下降(P<0.05)。初诊SAA组骨髓CD+4CD+25T细胞[(7.5±3.4)%]显著高于对照组[(4.3±0.9)%，P<0.05]，初诊SAA组及轻型再障(MAA)组骨髓CD+4CD+25/CD+4比值分别为(28.9±11.1)%和(28.2±9.4)%，均显著高于对照组[(17.4±0.9)%，P均<0.05]，骨髓TGF β1分别为(2.2±1.7)μg/L和(2.0±0.6)μg/L，均较对照组［(4.4±0.9)μg/L］显著降低(分别为P<0.01、P<0.05)，而Flt 3L水平分别为(1031.1±321.8)ng/L和(694.7±424.7)ng/L，均较对照组［(63.0±37.5)ng/L］显著增高(P均<0.01)。缓解期SAA儿童除外周血CD+8T细胞仍较对照组显著增高外，其余上述指标均接近正常水平。相关分析显示，骨髓CD+4CD+25T细胞与CD+3CD+4T细胞呈显著正相关(r分别为0.495、0.540,P<0.01)；Flt 3L与骨髓CD+3、CD+4、CD+8T细胞及CD+4CD+25T细胞均呈显著正相关(r分别为0.732、0.542、0.688、0.405,P分别<0.01、0.01、0.01、0.05)，而TGF β1与骨髓CD+8T细胞和Flt 3L水平呈显著负相关(r分别为-0.431、-0.482,P分别<0.05、<0.01)。结论儿童再障发病与CD+4CD+25T细胞数量缺乏无关，骨髓TGF β1水平显著降低和Flt 3L水平显著增高可能在再障儿童T淋巴细胞数量增多和功能紊乱中起重要作用。

Changes and significance of CD+4CD+25 regulatory T cells,transforming growth factor β1 and Flt 3 ligand in children with aplastic anemia.

AbstractObjectiveTo investigate the roles of immune regulatory T cells and cytokines in immune disorders in pediatric aplastic anemia(AA).MethodsLymphocyte subsets and CD+4CD+25 cells in bone marrow(BM) and peripheral blood(PB) were detected by FACS,and the levels of TGF β1 and Flt 3L in BM were measured by ELISA in 27 patients with idiopathic pediatric AA and controls.ResultsCompared to controls,the frequencies of CD+3CD+8 cells in BM and PB increased significantly in untreated AA patients,and the frequencies of NK in PB and B cells in BM decreased significantly in untreated SAA.The frequency of CD+4CD+25 cells in untreated SAA group [(7.5±3.4)%] was higher than that in controls [(4.3±0.9)%,P<0.05].The ratio of CD+4CD+25/ CD+4 in BM of untreated SAA group [(28.9±11.1)%] and MAA group [(28.2±9.4)%] was higher than that of controls [(17.4±0.9)%，P<0.05,respectively].The levels of TGF β1 in untreated SAA group [(2.2±1.7)μg/L] and MAA group [(2.0±0.6)μg/L] were lower than that in controls[(4.4±0.9)μg/L,P<0.01、<0.05,respectively].Flt 3L in SAA group [(1031.1±321.8)ng/L] and MAA group [(694.7±424.7)ng/L] was higher than that in controls[(63.0±37.5)ng/L,P<0.01,respectively].In recovered SAA patients treated by immunosuppressive therapy,all of the above but the frequency of CD+3CD+8 cells in PB returned to normal levels.There was significant positive relationship between CD+4CD+25 and CD+3,CD+3CD+4 cells (r=0.495,0.540,P<0.01,respectively),as well as between Flt 3L and CD+3,CD+3 CD+4,CD+3CD+8,CD+4CD+25 cells in BM(r=0.732,0.542,0.688,0.405,P<0.01,<0.01,<0.01,<0.05,respectively).Negative relations were found between TGF β1 and Flt 3L,CD+3CD+8 cells(r=-0.431,-0.482,P<0.05、<0.01,respectively).ConclusionThese results indicate that pediatric AA is not related to CD+4CD+25 regulatory T cells deficiency.The decreased TGF β1 and increased Flt 3L in BM may play an important role in T lymphocytes proliferation and function disorders in pediatric AA.