Abstract: 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.

Key words: Flt3 ligand, Child , Regulatory T cells, Transforming growth factorβ1

摘要： 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。

关键词: 再生障碍性贫血, 调节T细胞, 转化生长因子β1, Flt3配体, 儿童