宫颈上皮内瘤变及宫颈癌患者外周血Treg/Th17细胞及相关细胞因子的检测与临床意义

目的:探讨Treg/Th17平衡失调在宫颈上皮内瘤变(CIN)及宫颈癌病情进展中的作用及其参与CIN及宫颈癌免疫逃避的具体机制。方法:研究对象分为3组:宫颈癌组(34例),CIN组(47组),对照组(30例)。采用流式细胞术检测CIN及宫颈癌患者外周血单个核细胞(PBMC)中Th17细胞及Treg细胞的表达频率,采用酶联免疫吸附试验(ELISA)方法检测相关细胞因子(IL-23、IL-10、IL-17、IL-6、TGF-β)的浓度。结果:与对照组相比,Treg细胞及其相关细胞因子(TGF-β、IL-10)在CIN及宫颈癌患者外周血中的表达均明显增高(P<0.05),且宫颈癌组的表达亦明显高于CIN组(P<0.05)。与对照组相比,Th17细胞及其相关细胞因子(IL-23、IL-17、IL-6)在CIN及宫颈癌患者外周血中的表达均明显降低(P<0.05),且宫颈癌组的表达亦明显低于CIN组(P<0.05)。结论:随着CIN向宫颈癌的进展,Treg/Th17平衡向Treg细胞偏离,这一失衡参与了CIN的进展及宫颈癌的免疫逃避,其具体机制可能与二者在肿瘤免疫内环境相关的细胞因子调节有关。     

上皮性卵巢癌患者肿瘤局部微环境中Treg/Th17比例平衡的研究

目的:探讨上皮性卵巢癌(EOC)患者外周血、卵巢癌组织和癌旁腹膜中Treg/Th17是否存在失衡。方法:选取2011年9月至2013年12月同济大学第一妇婴保健院收治的16例EOC(EOC组)、11例良性上皮性肿瘤(良性肿瘤组)及14例健康成年女性(对照组),收集患者外周血并分离淋巴细胞;收集4例EOC患者腹水并分离淋巴细胞。流式细胞术检测外周血及腹水中Th17、Treg细胞占CD4+T细胞的比例。选取同一时间段在本院手术患者术中留取的卵巢肿瘤组织、腹膜组织及转移灶组织,包括13例EOC、16例EOC种植灶癌旁腹膜、5例良性卵巢肿瘤组织及腹膜,用免疫荧光染色分析Th17及Treg细胞在良性卵巢肿瘤、EOC原发灶和癌旁腹膜中的浸润情况。结果:(1)EOC患者外周血中Treg比例为(5.16±3.85)%,显著高于对照组[(2.41±1.76)%])和良性肿瘤组[(2.3873±2.336)%](P=0.025,P=0.043),后两组比较无统计学差异。EOC患者外周血中Th17细胞比例为(3.15±3.045)%,显著高于对照组[(1.22±1.13)%](P=0.044);良性肿瘤患者[(1.93±1.745)%]与EOC患者和对照组比较,差异均无统计学意义;Treg/Th17细胞比值在3组间均无统计学差异。EOC患者腹水与外周血中的Th17、Treg细胞比例及Treg/Th17比值比较,差异均无统计学意义(P0.05)。(2)EOC组肿瘤组织中Treg和Th17细胞比例及Treg/Th17比值分别为(0.1062±0.077)%、(0.143±0.056)%和0.80±0.56,与良性肿瘤组织[0%、(0.0789±0.11)%、0]比较,均显著增高(P均0.05)。(3)卵巢良性肿瘤腹膜中未见Treg及Th17细胞浸润,EOC腹膜种植灶癌旁腹膜中Treg、Th17细胞比例及Treg/Th17比值分别为(0.1024±0.1)%、(0.2254±0.23)%和0.8113±1.097,较良性肿瘤组均显著提高(P0.05)。(4)早期和晚期EOC组织中Th17、Treg比例以及Treg/Th17比值比较,差异均无统计学意义(P0.05)。结论:卵巢癌患者外周血Treg和Th17比例升高,但并未发现失衡。卵巢癌组织及癌旁腹膜微环境中存在失衡,这一失衡可能促进肿瘤增殖与迁移。     

子痫前期患者外周血中CD4^＋CD25^＋调节性T细胞水平及其意义

目的探讨子痫前期患者外周血CD4^＋ CD25^＋调节性T淋巴细胞（CD4^＋ CD25^＋Tr）和CD4^＋CD25^high调节性T淋巴细胞（CD4^＋ CD25^high Tr）在子痫前期发病中的作用。方法2005年10月至2006年3月对安徽省立医院子痫前期患者30例和正常早、晚期妊娠及正常非妊娠组妇女各13例、22例及15例,采用流式细胞仪检测其外周血CD4^＋ CD25^＋Tr和CD4^＋ CD25^highTr占CD4＋T细胞的比率,分析其与子痫前期的关系。结果子痫前期组妇女外周血CD4^＋CD25^＋Tr和CD4^＋ CD25^highTr表达率分别为（6.64±1.10）%和（0.53±0.17）%,明显低于正常晚期妊娠组妇女的（12.26±1.32）%和（1.18±0.05）%,两组比较,差异有统计学意义（P〈0.01）。正常非妊娠组妇女外周血CD4^＋ CD25^＋Tr表达率（10.8±1.05）%和正常早期妊娠组CD4^＋ CD25^＋Tr表达率（11.21±1.40）%比较,差异无统计学意义,但均低于正常晚期妊娠组（P〈0.05）。结论CD4^＋ CD25^＋Tr和CD4^＋ CD25^highTr可能与子痫前期的发病机制有关。     

子前期患者外周血中CD4~+ CD25~+调节性T细胞水平及其意义

目的探讨子前期患者外周血CD4+ CD25+调节性T淋巴细胞(CD4+ CD25+Tr)和CD4+CD25high调节性T淋巴细胞(CD4+ CD25highTr)在子前期发病中的作用。方法2005年10月至2006年3月对安徽省立医院子前期患者30例和正常早、晚期妊娠及正常非妊娠组妇女各13例、22例及15例,采用流式细胞仪检测其外周血CD4+ CD25+Tr和CD4+ CD25highTr占CD4+T细胞的比率,分析其与子前期的关系。结果子前期组妇女外周血CD4+CD25+Tr和CD4+ CD25highTr表达率分别为(6.64±1.10)%和(0.53±0.17)%,明显低于正常晚期妊娠组妇女的(12.26±1.32)%和(1.18±0.05)%,两组比较,差异有统计学意义(P<0.01)。正常非妊娠组妇女外周血CD4+ CD25+Tr表达率(10.8±1.05)%和正常早期妊娠组CD4+ CD25+Tr表达率(11.21±1.40)%比较,差异无统计学意义,但均低于正常晚期妊娠组(P<0.05)。结论CD4+ CD25+Tr和CD4+ CD25highTr可能与子前期的发病机制有关。     

Th17细胞在妇产科疾病中作用研究进展

<正>T淋巴细胞是人体内免疫系统的重要组成部分,CD4+T细胞作为效应T细胞的重要成员之一,过去将CD4+T细胞分为Th1和Th2两类细胞亚群[1]。Th1细胞主要介导细胞免疫,主要分泌白细胞介素2(IL-2)、肿瘤坏死因子β(TNF-β)、干扰素γ(IFN-γ)等。其中IFN-γ占主导地位,具有诱导肿瘤细胞凋亡、抑制血管生成,激活抗肿瘤活性的作用。尤其是在细菌、病毒及原虫感染中起保护作用[2]。Th2细胞主要分泌IL-4、IL-5、IL-10和IL-13,介导体液免疫反应。其中IL-4和IL-5起主要作用,其     

卵巢早衰患者外周血CD4~+CD25~+Treg细胞的变化及意义

目的:探讨CD4+CD25+调节性T细胞(即CD4+CD25+Treg细胞)在卵巢早衰发病机制中的作用。方法:流式细胞仪定量检测卵巢早衰(premature ovarian failure,POF)患者、卵巢储备功能下降(diminished ovarian reserve,DOR)患者及健康对照组外周血CD4+T、CD8+T细胞及CD4+CD25+Treg细胞数量,应用3H-thymidine掺入法测定POF患者及对照组外周血CD4+CD25+Treg细胞对效应性T细胞的增殖抑制功能。结果:与对照组相比,POF患者及DOR患者CD4+CD25+Treg细胞比例降低(P<0.01)、POF患者CD4+T/CD8+T细胞比值增高(P<0.05),DOR患者CD4+T/CD8+T细胞比值无明显变化(P>0.05);POF患者免疫抑制功能无明显降低(P>0.05)。结论:CD4+CD25+Treg细胞比例降低与T细胞亚群失衡可能是POF的发病机制。     

Th1/Th2比率变化与子痫前期相关性研究

目的:探讨Th1/Th2比率变化与子痫前期相互关系.方法:采用流式细胞技术分别检测15例正常妊娠孕妇(正常妊娠组)和40例子痫前期患者(子痫前期组)外周血和蜕膜组织中的Th1、Th2及Th1/Th2细胞比率,同时测定其肝、肾功能.结果:①子痫前期组Th1细胞、Th1/Th2比率明显高于正常妊娠组(P<0.01);②外周血Th1/Th2比率与蜕膜Th1/Th2比率间呈显著正相关(r=0.818,P<0.01);③Th1细胞、Th1/Th2比率与肝、肾功能损害呈正相关,且随病情的严重程度有升高趋势.结论:子痫前期患者局部的Th1/Th2比率平衡被打乱,Thl/Th2比率改变可能是其发病的重要原因,在一定程度上也反映了病情的轻重.     

子前期患者外周血中CD4+CD25+调节性T细胞水平及其意义

目的 探讨子(癎)前期患者外周血CD4+CD25+调节性T淋巴细胞(CD4+CD25+Tr)和cD4+CD25high 调节性T淋巴细胞(CD4+ CD25high Tr)在子(癎)前期发病中的作用.方法 2005年10月至2006年3月对安徽省立医院子(癎)前期患者30例和正常早、晚期妊娠及正常非妊娠组妇女各13例、22例及15例,采用流式细胞仪检测其外周血CD4+CD25+Tr和CD4+CD25high Tr占CD4+T细胞的比率,分析其与子(癎)前期的关系.结果 子(癎)前期组妇女外周血CD4+CD25+Tr和CD4'cD25 highrrr表达率分别为(6.64±1.10)%和(0.53±0.17)%,明显低于正常晚期妊娠组妇女的(12.26±1.32)%和(1.18±0.05)%,两组比较,差异有统计学意义(P＜0.01).正常非妊娠组妇女外周血CD4+CD25'Tr表达率(10.8±1.05)%和正常早期妊娠组CD4'CD25'Tr表达率(11.21±1.40)%比较,差异无统计学意义,但均低于正常晚期妊娠组(P＜0.05).结论 CD4+CD25+Tr和CD4+cD25high Tr可能与子(癎)前期的发病机制有关.     

垂体抑制对冻融胚胎不明原因反复胚胎植入失败患者Th17/Treg细胞失衡的影响

目的:探讨垂体抑制对冻融胚胎不明原因反复胚胎植入失败(uRIF)患者外周血辅助性T细胞17(Th17)和调节性T(Treg)细胞平衡的影响及其降调的可能机制。方法:选择82例35岁以下冻融胚胎uRIF的患者,其中46例单纯激素替代治疗(HRT)为HRT组,36例HRT联合促性腺激素释放激素激动剂(GnRHa)降调为GnRHa降调组,选择正常妊娠早期妇女50例作为对照组。采用流式细胞术(FCM)检测HRT组和GnRHa降调组在HRT备内膜前以及黄体酮转化日外周血中Th17、Treg细胞及Th17/Treg细胞比值,并与对照组比较。结果:与对照组相比,HRT前Th17百分比在GnRHa降调组和HRT组中均升高;Treg细胞百分比均降低,Th17/Treg细胞比值均升高(P0.05),Th17/Treg细胞平衡向Th17转移。与HRT前相比,黄体酮转化日HRT组和GnRHa降调组Th17百分比降低(P0.05),Treg细胞百分比升高(P0.05);黄体酮转化日GnRHa降调组Th17/Treg细胞比值较HRT组明显降低(P0.05),Th17/Treg细胞平衡向Treg细胞转移。GnRHa降调组雌二醇(E_2)水平略高于HRT组,差异无统计学意义(P0.05)。结论:uRIF患者Th17和Treg细胞数量分别增加和减少,Th17/Treg细胞比值失衡。GnRHa降调可能通过阻断Th17/Treg细胞比值失衡对子宫内膜容受性发挥免疫调节作用,并且这些效应不依赖于外周血中的雌激素水平。     

CD4+CD25+调节性T细胞在妊娠免疫耐受中的研究

免疫抑制是母体成功妊娠必需的,近来研究认为CD4+CD25调节性T细胞(Treg)是免疫抑制机制中的关键成分.该类细胞是Treg的重要亚群,在体内自然存在,能分泌白细胞介素10(IL-10)、转化生长因子-β(TGF-β),表达IL-2Rα(CD25),细胞毒性T淋巴细胞抗原4(CTLA-4)分子等.在早、中期妊娠,母体全身和蜕膜的CD4+CD25Treg比率明显增加,通过细胞直接接触的方式抑制效应性T细胞的活性及分泌抑制性细胞因子等,可能在人类妊娠中扮演重要的角色.     

儿童急性白血病外周血Th17细胞表达及其临床意义分析

摘要：目的　探讨辅助性T细胞17（Th17）细胞表达与儿童急性白血病的发生发展及疾病状态的关系。方法　将2008年8月至2009年12月在华中科技大学同济医学院附属协和医院儿科住院的42例急性白血病患儿分为未缓解组（A组,23例）和缓解组（B组,19例）。18名健康儿童作为对照组（C组）。采用酶联免疫吸附法（ELISA法）检测各组外周血单个核细胞（PBMC）刺激培养上清液中白细胞介素-17（IL-17）和白细胞介素-23（IL-23）的水平,利用流式细胞术分析PBMC中CD4+ IL-17+细胞的比例。结果　A组和B组IL-17和IL-23均低于C组,差异有统计学意义（P < 0.05）,A组IL-17低于B组,差异具有统计学意义（P < 0.05）,但两组IL-23差异无统计学意义（P ＞ 0.05）。A组和B组Th17的比例均低于C组,且A组Th17低于B组,差异均具有统计学意义（P均< 0.05）。结论　Th17细胞可能通过分泌IL-17参与了儿童急性白血病发生及病情发展,其水平高低部分反映白血病的疾病状态。     

Changes of Th17/Tc17 and Th17/Treg cells in endometrial carcinoma

Objectives

T helper 17 (Th17), T cytotoxic 17 (Tc17) and regulatory T (Treg) cells are important factors in the pathogenesis of inflammatory and autoimmune diseases. However, information concerning the roles of these cells in antitumor immunity or endometrial tumorigenesis remains limited. In this study, we aimed to describe the distribution of Th17, Tc17 and Treg cells in endometrial carcinoma patients, and elucidate the probable role of these effector T cells.

Methods

We assessed the expression of interleukin (IL)-17 and Foxp3 in the peripheral blood of endometrial carcinoma patients and healthy controls by flow cytometry to determine the relative numbers of Th17, Tc17 and Treg cells. Th17 cells and Tc17 cells were counted as percentages of the total number of CD3⁺ T cells; Treg cells were counted as a percentage of the total number of CD4⁺ T cells. We also evaluated Th17 and Tc17 cells in tumor tissue by immunohistochemical staining. IL-17 and IL-10, dominant products of these three cell types, were detected by using enzyme-linked immunosorbent assays.

Results

The frequencies of Th17, Tc17 and Treg cells, as well as the serum level of IL-10, were significantly elevated in endometrial carcinoma patients compared to healthy controls. The Th17/Tc17 and Th17/Treg ratios were also observed to change significantly. However, there was no significant difference on the IL-17 levels in the serum. Additionally, immunohistochemistry performed on tumor tissues indicated that the amounts of Th17 and Tc17 increased in the cancer patients.

Conclusions

Our data suggests a probable involvement of Th17, Tc17 and Treg cells in the pathogenesis of endometrial carcinoma. Restoring the balance of these cells may help with the research and development of immunotherapies for endometrial carcinoma.     

Expression imbalance of IL-17/IL-35 in peripheral blood and placental tissue of pregnant women in preeclampsia

ObjectivesThe possible mechanism of preeclampsia is investigated in this study to facilitate the exploration of the future remediation of this disease by analysing the changes of IL-17 and IL-35 in peripheral blood and placental tissue of pregnant women with preeclampsia (PE).Materials and methodsThe study was conducted using 45 healthy pregnant women as the control group and 90 pregnant women in the preeclampsia group, including 45 cases with severe preeclampsia and 45 cases with mild preeclampsia. All of 135 pregnant women underwent caesarean delivery. IL-17 and IL-35 concentrations in the serum were measured by ELISA, and IL-17 and IL-35 expression in placental specimens was detected by immunohistochemistry.ResultsThere were no statistically significant differences in age among the three study groups. Serum IL-17 levels were significantly higher in PE patients than in healthy pregnant women (P < 0.01). The ratio of positive staining for IL-17 was markedly higher in mild PE tissues (84.44%; 38/45) and severe PE tissues (86.67%; 39/45) than in healthy pregnant tissues (35.56%; 16/45) (P < 0.01). The strong positive rates for IL-17 were markedly higher in mild PE tissues (48.89%; 22/45) and severe PE tissues (68.89%; 31/45) than in healthy pregnant tissues (13.33%; 6/45) (P < 0.01). No differences between mild PE tissues and severe PE tissues were noted in both positive case rates and strong positive rates. Consistent with this finding, the ratio of strong positive staining for IL-35 was higher in healthy pregnant tissues (66.67%; 30/45) than in mild PE tissues (33.11%; 14/45) and severe PE tissues (26.67%; 12/45) (P < 0.01).ConclusionsThe abnormal increase in serum and placental of IL-17 has an association with the formation and development of PE. IL-35 expression is significantly lower in severe PE placenta tissue and serum compared with normal pregnant women. These results suggested that IL-17/IL-35 imbalance may play a role in the pathophysiology of PE.     

原因不明复发性流产与蜕膜CD4~+ CD25~+ T调节细胞和CD8~+ CD28~- T细胞的关系

目的:探讨原因不明复发性流产(unexplained recurrent spontaneous abortion,URSA)与蜕膜CD4+ CD25+ T细胞和CD8+ CD28-T细胞的关系。方法:采用流式细胞四色荧光法,检测原因不明复发性流产17例(URSA组)和正常早孕人流20例(对照组)的蜕膜CD4+ CD25+ T细胞及其FoxP3(+)表达,CD8+ CD28- T细胞及其表面CD95、CD95L表达。结果:两组蜕膜中CD4+ CD25+ T细胞比例无明显差异(P>0.05),URSA组蜕膜CD4+ CD25+ T细胞中FoxP3阳性率明显低于对照组(P<0.0001)。两组蜕膜CD8+ CD28- T细胞比例及其细胞表面CD95和CD95L的阳性表达率均无明显差异(P>0.05);结论:蜕膜CD4+ CD25+ FoxP3(+)T调节细胞明显减少,是导致URSA患者母胎界面免疫耐受异常的重要原因。     

Th1, Th2, Th17 and Treg levels in umbilical cord blood in preeclampsia

Introduction: Preeclampsia is one of the major causes of maternal and neonatal mortality. During pregnancy, the immune system must maintain the tolerance to the fetus, thus changes in the cytokine balance may result in a disturbed pregnancy. T helper cells play an important role in modulation of the immune system and are involved in this cytokine balance.

Objective: Many studies have been performed to study the T cell composition in different compartments during pregnancy, although this is the first study in which T cells are evaluated in umbilical cord blood.

Study design: Intracellular expression of INF-gamma, IL-17, IL-4 and forkhead foxP3 in CD4+ T cells was evaluated in umbilical blood from healthy pregnant and preeclamptic women using a flow cytometer.

Results: Th2 and Treg cells levels were significantly diminished in preeclamptic compared to the healthy women, but no difference in Th1 and Th17 levels were found between both groups.

Conclusions: Our data suggest that the cytokine balance is broken, encouraging the development of an exacerbated inflammatory response. Our results show that there is a shift, in the Th1/Th2, and the Th17/Treg balance, favoring skewness towards a proinflammatory status in the umbilical cord blood in preeclampsia.     

Foxp3在子宫内膜、正常早孕和原因不明复发性流产患者蜕膜上的表达

目的:探讨Foxp3在增生期、分泌期内膜和正常早孕、原因不明复发性流产(URSA)患者蜕膜的表达。方法:用免疫组化法观察15例增生期子宫内膜, 12例分泌期子宫内膜, 32例正常早孕和25例URSA患者蜕膜组织Foxp3的表达与分布。结果:增生期子宫内膜无Foxp3表达,分泌期内膜和蜕膜组织均有表达;分泌期内膜Foxp3的表达显著低于正常早孕组(P<0 .01)和URSA组(P<0. 05);URSA患者蜕膜Foxp3的表达显著低于正常早孕组(P<0 .01);Foxp3表达于胞浆,正常早孕组和分泌期内膜主要表达在腺上皮细胞,URSA患者主要表达在间质细胞。结论:Foxp3在分泌期子宫内膜和蜕膜组织的表达可能在胚泡植入和早期妊娠的维持中起重要作用,其表达水平降低可能与URSA的发生有关。     

泼尼松治疗原发性肾病综合征对患儿CD4+CD25+调节性T细胞的影响分析

目的　观察原发性肾病综合征（PNS）患儿泼尼松治疗前后CD4+CD25+ 调节性T细胞（CD4+CD25+ Tr）的变化,阐明肾上腺糖皮质激素治疗儿童PNS的免疫机制。方法　选择2004—2007年在深圳市儿童医院住院治疗的初发PNS患儿42例,其中激素敏感型32例,激素耐药型10例。同期25例健康体检儿童作为对照组。流式细胞术检测泼尼松治疗前后外周血CD3+CD4+CD8-、CD3+CD4-CD8+、CD4+CD25+Tr的比例,荧光定量聚合酶链反应（Real-time PCR）检测泼尼松治疗前后外周血单个核细胞（PBMC）叉头型基因P3（Foxp3）、细胞毒性T淋巴细胞相关抗原4（CTLA-4）和糖皮质激素诱导的肿瘤坏死因子受体 （GITR）基因mRNA的表达。结果 　与对照组比较,PNS患儿外周血CD3+CD4+CD8- T细胞、CD3+CD4-CD8+ T细胞、CD4+CD25+ Tr比例无明显改变（P > 0.05）。激素敏感型PNS患儿CD4+CD25+Tr比例在泼尼松治疗后明显增高,差异有统计学意义（P < 0.01）;激素耐药型PNS患儿CD4+CD25+Tr比例在泼尼松治疗前后无明显改变（P > 0.05）。激素敏感型PNS患儿在泼尼松治疗后PBMC细胞Foxp3、CTLA-4和GITR基因mRNA的表达明显增高;而激素耐药型PNS患儿泼尼松治疗前后Foxp3、CTLA-4基因表达无明显改变,仅GITR表达明显增高。 结论 泼尼松等肾上腺糖皮质激素类药物可通过上调激素敏感型PNS患儿CD4+CD25+调节性T细胞的表达发挥免疫治疗作用。     

Expression and significance of dendritic cells and Th17/Treg in serum and placental tissues of patients with intrahepatic cholestasis of pregnancy

Purpose: Dendritic cells (DCs) are involved in immune system, which can also regulate the differentiation of T helper 17 (Th17) and regulatory T cells (Treg). DCs and Th17/Treg participate in preeclampsia and recurrent spontaneous abortion (RSA), but there is still lack of research in intrahepatic cholestasis of pregnancy (ICP). The aim was to evaluate the expression and significance of CD83⁺DCs, CD1a⁺DCs, interleukin-17 (IL-17) and IL-35 in serum and placental tissues of patients with ICP.

Methods: Thirty cases of mild ICP, 25 cases of severe ICP were selected, and 30 cases of normal pregnant women were selected as control group. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) were used to detect the expression of CD83⁺DCs, CD1a⁺DCs, IL-17 and IL-35 in serum and placenta tissues, respectively.

Results: There were more CD83⁺DCs, IL-17 expressed in placenta from women with ICP than in normal pregnancies, while the number of decidual CD1a⁺DCs, IL-35 was significantly lower in ICP than in normal pregnant women. The comparison within three groups had statistical difference (p?+DCs and CD1a⁺DCs levels had no significance. IL-17 was higher in ICP, while IL-35 was lower.

Conclusions: DCs are involved in damaging the maternal–fetal immune tolerance by changing the phenotype and mature state, which may affect the differentiation of Th17/Treg to cause ICP.     

CD4~+CD25~+FOXP3~+调节性T淋巴细胞数量及功能变化与子宫内膜异位症患者发病相关性研究

目的:分析子宫内膜异位症(EMs)患者在位、异位内膜及外周血内CD4~+CD25~+FOXP3~+调节性T淋巴细胞(Treg细胞)的数量、分布及功能特性,探讨Treg细胞与EMs发病之间的关系。方法:收集EMs患者在位、异位内膜组织及外周血标本,并以非内异症患者作为对照,免疫组化分析在位、异位内膜内叉头状/翅膀状螺旋转录因子3(FOXP3)阳性细胞的数量及分布变化情况,并与EMs患者的r AFS临床分期进行相关性分析。流式细胞术检测Treg细胞占外周血CD4~+T淋巴细胞的百分比,及磁珠分选外周血内CD4~+CD25~+T细胞及CD4~+CD25-T细胞,3H-thymidine法测定CD4~+CD25~+T细胞免疫抑制功能变化情况。结果:EMs、非EMs患者在位内膜内平均FOXP3阳性细胞密度并无显著差异[(76.44±62.14)/mm~2vs(50.59±20.79)/mm~2;WU=152.0,P=0.20]。进一步按月经周期行亚组分析:EMs分泌期内膜内FOXP3阳性细胞密度显著高于非EMs患者[(94.84±53.91)/mm~2vs(31.37±19.02)/mm~2;MU=43.00,P=0.03]。不同r AFS期别患者卵巢异位症病灶内FOXP3阳性细胞密度并无显著差异[I~II期:(123.00±115.00)/mm~2vs III~IV期:(111.00±108.00)/mm~2;MU=139.5,P0.05]。EMs患者外周血内Treg细胞比例显著低于非EMs患者[(0.58±0.21)%vs(1.35±0.38)%,P0.001],但EMs患者外周血CD4~+CD25~+T淋巴细胞对CD4~+CD25-T淋巴细胞增殖抑制率,与非EMs相比并无显著变化[(68.43±18.15)%vs(66.37±17.78)%,P0.05]。结论:EMs患者在位内膜内Treg细胞失去正常的周期波动性,EMs患者分泌期内Treg细胞数目增加可能与内异症发病相关。EMs患者外周血内Treg细胞比例下降,但其免疫抑制功能并无明显改变。