CAJ | 학술논문

目的对初发系统性红斑狼疮(SLE)患者外周血异常表达CD4+CD25-Foxp3+T淋巴细胞进行表型鉴定,并探讨其临床意义.方法对初发SLE患者外周血CD4+T淋巴细胞进行细胞表面分子[CD25、CD127、CCR4、糖皮质激素诱导的肿瘤坏死因子受体(GITR)、细胞毒T淋巴细胞相关抗原4(CT-LA-4)]和胞内分子(Foxp3)标染,流式细胞仪检测,并研究CD4+各细胞亚群与狼疮肾炎和疾病活动度(SLEDAI)相关性.结果 SLE患者外周血CD4+CD25-Foxp3+T淋巴细胞表面 GITR、CTLA-4和CCR4表达率与活化T淋巴细胞(CD4+CD25+Foxp3-)相比差异无统计学意义(P均>0.05),而显著低于调节性T淋巴细胞(CD4+CD25+Foxp3+)(P均<0.01);CD4+Foxp3+CD25high,CD4+Foxp3+CD25low和CD4+Foxp3+CD25-细胞中CD127low-百分率分别为(93.8±,3.5)%,(93.7±2.3)%,(92.0±2.1)%,三者之间差异无统计学意义(P>0.05);在CD4+细胞亚群中,当CD127low-时,Foxp3+在CD25high,CD25low和CD25-中表达率分别为 (91.4±2.6)%,(71.9±3.3)%,(9.0±2.2)%,三者之间差异均有统计学意义(P<0.01);SLE患者外周血CD4+CCR4+CD25highT淋巴细胞百分率与SLEDAI呈显著负相关(r=-0.695,P<0.001),狼疮肾炎患者(1.10±0.17)%显著低于SLE无肾炎组[(1.61±0.23)%,P<0.01]和健康对照组[(1.75±0.10)%,P<0.01];狼疮肾炎患者外周血CD4+ CCR4+CD25low-T淋巴细胞百分率显著高于健康对照组[(11.5 ±2.3)%与(8.0±1.0)%,P<0.01)].结论初发SLE中异常升高的CD4+CD25-Foxp3+T淋巴细胞的表型类似早期活化效应T淋巴细胞.可以用CD4+CD25highCD127low-T淋巴细胞替选CD4+CD25highFoxp3+调节性T淋巴细胞.CCR4+调节性T淋巴细胞可能参与狼疮肾炎发病.
목적 대초발계통성홍반랑창(SLE)환자외주혈이상표체CD4+CD25-Foxp3+T림파세포진행표형감정,병탐토기림상의의.방법 대초발SLE환자외주혈CD4+T림파세포진행세포표면분자[CD25、CD127、CCR4、당피질격소유도적종류배사인자수체(GITR)、세포독T림파세포상관항원4(CT-LA-4)]화포내분자(Foxp3)표염,류식세포의검측,병연구CD4+각세포아군여랑창신염화질병활동도(SLEDAI)상관성.결과 SLE환자외주혈CD4+CD25-Foxp3+T림파세포표면 GITR、CTLA-4화CCR4표체솔여활화T림파세포(CD4+CD25+Foxp3-)상비차이무통계학의의(P균>0.05),이현저저우조절성T림파세포(CD4+CD25+Foxp3+)(P균<0.01);CD4+Foxp3+CD25high,CD4+Foxp3+CD25low화CD4+Foxp3+CD25-세포중CD127low-백분솔분별위(93.8±,3.5)%,(93.7±2.3)%,(92.0±2.1)%,삼자지간차이무통계학의의(P>0.05);재CD4+세포아군중,당CD127low-시,Foxp3+재CD25high,CD25low화CD25-중표체솔분별위 (91.4±2.6)%,(71.9±3.3)%,(9.0±2.2)%,삼자지간차이균유통계학의의(P<0.01);SLE환자외주혈CD4+CCR4+CD25highT림파세포백분솔여SLEDAI정현저부상관(r=-0.695,P<0.001),랑창신염환자(1.10±0.17)%현저저우SLE무신염조[(1.61±0.23)%,P<0.01]화건강대조조[(1.75±0.10)%,P<0.01];랑창신염환자외주혈CD4+ CCR4+CD25low-T림파세포백분솔현저고우건강대조조[(11.5 ±2.3)%여(8.0±1.0)%,P<0.01)].결론 초발SLE중이상승고적CD4+CD25-Foxp3+T림파세포적표형유사조기활화효응T림파세포.가이용CD4+CD25highCD127low-T림파세포체선CD4+CD25highFoxp3+조절성T림파세포.CCR4+조절성T림파세포가능삼여랑창신염발병.
Objective To compare the phenotypes of abnormal CD4+CD25-Foxp3+ T cells with traditional regulatory T cells (CD4+CD25+Foxp3+) in patients with untreated new-onset lupus (UNoL) and investigate their clinical relevance. Methods The expressions of surface markers (CD25, CD127, CCR4, GITR, CTLA-4) and intracellular marker(Foxp3) on the peripheral blood mononuclear cells from twenty-two UNoL patients were analyzed by flow cytometry analysis, and their clinical relevance were assessed. Results There were no significant differences between CD4+CD25-Foxp3+ and CD4+CD25+Foxp3- T cells in the expressions of GITR, CTLA--4 and CCR4 (P>0.05), but they were significantly lower than those of CD4+CD25+ Foxp3+ T cells in UNoL patients (P<0.01). The percentages of CD127low- in CD4+Foxp3+CD25high,CD4+Foxp3+ CD25low and CD4+Foxp3+CD25+ T cells were (93.8±3.5 )%, (93.7±2.3)% and (92.0±2.1)% respectively (P> 0.05), whereas the expressions of Foxp3 on CD4+CD127low- T subpopulations showed significant differences in CD4+CDI27low-CD25high (91.4±2.6)%, CD4+CD127low-CD25low (71.9±3.3)% and CD4+CD127low-CD25- (9.0± 2.2)% T cells(P<0.01 ). The frequency of CD+CCR4+CD25high T cells correlated negatively with SLEDAI (r=-0.695,P<0.001).and it was significantly lower in lupus nephritis patients(1.10±0.17)%compared with SLE patients without nephritis [(1.61±0.23)%,P<0.01]and healthy controls [(1.75±0.10)%,P<0.01], furthermore,the frequency of CD4+CCR4+CD25low-T cells in lupus nephritis was significantly higher than that in healthy controls[(11.5±2.3)%vs (8.0±1.0)%,P<0.01].Conclusion The increased CD4+CD25-Foxp3+ T cells in the Untreated Newonset Lupus(UNoL)patients mimic activated T effector cells.CD4+CD25high-CD127low-T cells can be used to isolate live CD4+CD25highFoxp3+regulatory T cells.CCR4+regulatory T cells may be involved in the pathogenesis of lupus nephritis.