妊娠期调节性T细胞介导保护性效应需要同种抗原的刺激  

Alloantigen stimulation is indispensable to the immuno-protective effect mediated by the regulatory T cells during pregnancy

作　　者：肇静娴[1] 曾耀英[1] 刘毅[2] 

机构地区：[1]暨南大学组织移植与免疫教育部重点实验室,广州510632 [2]中国协和医科大学皮肤病研究所病理科,南京210042

出　　处：《现代免疫学》2006年第3期226-230,共5页Current Immunology

基　　金：国家自然科学基金面上项目(30500466);广东省自然科学基金博士启动项目(05300419);暨南大学引进优秀人才科研启动基金项目(51204065)

摘　　要：越来越多的证据表明,人和小鼠妊娠期CD4+CD25+调节性T细胞(Treg)参与介导母胎免疫耐受。然而,目前对于妊娠期间调控Treg变化的因素还不清楚,对同基因交配(BALB/c×BALB/c)和异基因交配(BALB/c×C57)小鼠以及妊娠妇女CD4+CD25+Treg进行了分析,以探讨雌、孕激素和胎儿同种异基因抗原对Treg的影响。发现异基因孕鼠外周淋巴器官CD4+CD25+T细胞于早孕、中孕期明显高于非孕对照,而在同基因孕鼠只有少数个例升高;这些CD4+CD25+T细胞均表达Foxp3蛋白,在体外具有无反应性和免疫抑制能力;而且异基因孕鼠淋巴细胞对父方同种抗原的应答强度明显弱于同基因孕鼠。对去势的雌鼠给予雌二醇或孕酮,使其在血清中浓度接近中孕水平,未发现外周血CD4+CD25+Treg的明显变化。妊娠妇女CD4+CD25highTreg在早孕、中孕期显著升高,临近分娩期降至非孕水平,而此时CD4+CD25lowT细胞反而增加。以上结果表明,异基因抗原的存在对于妊娠期CD4+CD25+Treg介导对胎儿的免疫保护效应具有重要作用,而CD4+CD25+Treg的消失可能与分娩的发动有一定关系。More and more evidences suggest that CD4^＋CD25^＋ regulatory T cells （Treg） participate the development of maternal tolerance to fetus in pregnancies of both humans and mice, howver, the factors controlling the activities of Treg during pregnancy are poorly understood. In the present study, the CD4^＋CD25^＋ Treg cells were analysed in the syngeneic pregnant mice （BALB/c×BALB/c）, allogeneic pregnant miee（BALB/c×C57BL/c） and pregnant women to investigate the influence of estrogen, progesterone and the allogencie antigens of fetus on the activities of Treg cells, h was demonstrated that the frequency of CD4^＋CD25^＋ T cells in peripheral lymphoid organs of the allogeneic pregnant mice were increased during the first and second trimester of gestation in comparison with those of the non-pregnant controls, hut it increased only in small number of eases of the syngeneic pregnant mice. All these CD4^＋CD25^＋T cells expressed Foxp3 protein as demonstrated by intracellular staining, and showed properties of anergy and immunosuppression in vitro. Morever, the allergenic pregnant mice exhibited reduced responses to the paternal alLoantigens than the syngeneic pregnant mice, No difference in frequency of the circulating Treg cells in ovariectomized mice could he observed, when estrogen or progesterone was given to the female mice so as to make the serum concentrations of these agent approaching to the mid-gestation level. The numbers of CD4^＋CD25^kigh Treg cells in pregnant women were found to he increased during the first and second trimester, but it decreased to normal level at the end of pregnancy, while those of the CD4^＋CD25^low increased on the contray. These results suggest that the existence of the allogeneic antigens is of significant importance for the immuno-protcctive, effect mediated by the regulatory T cells during prcgnaney, and the disappearance of these cells may contribute to the induction of lahor.

关 键 词：妊娠 CD4+CD25+调节性T细胞 同种异基因抗原 FOXP3 雌二醇 孕酮 

分 类 号：R392.4[医药卫生—免疫学] R392.9[医药卫生—基础医学]