正常妊娠妇女外周血可溶性白细胞介素－2受体及淋巴细胞亚群的变化

测定了８７例妊娠晚期及２９例正常非孕妇女外周血可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）水平，同时对其中３６例孕妇及１０９例正常非孕妇女（正常对照）进行外周血淋巴细胞亚群检测。结果：妊娠晚期妇女ｓＩＬ－２Ｒ水平及Ｔｓ细胞（ＣＤ＿８）明显高于正常对照，分别为：２１４６００±７０４００Ｕ／Ｌ比１６２１００±８４１Ｄ０Ｕ／Ｌ，　Ｐ＜０．０１及３７．６％±５．３％比３１．３％±７．０％，Ｐ＜０．０１。妊娠妇女Ｔｈ细胞／Ｔｓ细胞（ＣＤ＿４／ＣＤ＿８）比例明显低于正常对照（１．２±０．２比１．５±０．５，Ｐ＜０．０１）。但总Ｔ淋巴细胞（ＣＤ＿３），ＣＤ＿４，细胞与正常对照相比，差异无显著性，分别为：６４．１％±７．３％比６６．０％±９．９％，Ｐ＞０．０５及４４．１％±５．８％比４３．８％±９．Ｏ％，Ｐ＞０．０５。相关分析表明孕妇ｓＩＬ－２Ｒ水平与ＣＤ＿３、ＣＤ＿４、ＣＤ＿８细胞及ＣＤ＿４／ＣＤ＿８均无显著相关性（ｒ分别为０．２０３２，０．２０７７，０．１０３７及０．１２１４，Ｐ均＞０．０５）。提示：孕妇外周血Ｔ淋巴细胞亚群及血清ｓＩＬ－２Ｒ的变化对维持正常妊娠有重要作用，ｓＩＬ－２Ｒ可能是促进胎儿正常生长的重要介质之一。     

野生型p53基因对人卵巢癌细胞株的生长抑制作用

目的：探讨野生型ｐ５３(ｗｔ ｐ５３)基因对人卵巢癌细胞株的生长抑制作用。方法：利用脂质体介导，将含有人全长ｗｔ－ｐ５３基因ｃＤＮＡ的真核表达载体质粒ｐＣＥＰ４／ｐ５３和空载体质粒ｐＣＥＰ４分别转染卵巢癌ＳＫＯＶ３细胞株，分别命名为ＳＫＯＶ３－ｐＣＥＰ４／ｐ５３细胞(C组)、ＳＫＯＶ３－ｐＣＥＰ４细胞(B组)，另设ＳＫＯＶ３细胞为正常对照组（Ａ组）。观察细胞体外生长情况和凋亡变化。结果：外源性ｐ５３基因在Ｃ组细胞中获表达，细胞生长曲线显示ｐ５３的导入使ＳＫＯＶ３细胞生长受到明显抑制，Ｃ组平均细胞集落数（１８．６±１．８个）少于Ａ组（２４．３±２．２个）和Ｂ组（２２．７±２．６），差异有显著性（Ｐ（005）。ＭＴＴ法检测C组细胞活力明显低于Ａ、Ｂ组。Ｃ组细胞Ｇ０～Ｇ１期百分比（５７．７９％）及凋亡细胞百分比（13．９1％）均高于Ｂ组（４６．０２％、２．０８％）和Ａ组（４３．６２％、０）。结论：ｗｔ－ｐ５３基因可介导ＳＫＯＶ３细胞Ｇ１期停滞和细胞凋亡，抑制细胞体外生长。     

成人型多囊肾病产前基因诊断一例

成人型多囊肾病（ＡＰＫＤ）是人类最常见的一种多系统危害严重的单基因遗传病，目前尚无有效的预防和根治措施，产前诊断可预防该病患儿的出生。ＰＫＤ１基因定位于１６ｐ１３３，我们用与ＰＫＤ１紧密连锁的４个微卫星ＳＭ６、ＣＷ４、ＣＷ２和ＫＧ８等对一ＡＰＫＤ家...     

卵巢上皮性癌肿瘤浸润淋巴细胞与腹水中肿瘤相关淋巴细胞生物学特性的比较

目的比较卵巢上皮性癌肿瘤浸润淋巴细胞（ＴＩＬ）及腹水中肿瘤相关淋巴细胞（ＴＡＬ）的生物学特性。方法收集１２例上皮性卵巢癌组织及腹水，并将其分为实体瘤、血性腹水和非血性腹水３组。将３组标本分别在体外进行ＴＩＬ及ＴＡＬ分离，并在自体肿瘤细胞（ＡＴＣ）以及重组白细胞介素２（ｒＩＬ２）存在的条件下共同培养。其间应用流式细胞仪及４小时５１Ｃｒ释放实验分别测定每组标本的淋巴细胞表型及其抗肿瘤活性。结果３组淋巴细胞具有相似的ＣＤ３、ＣＤ４、ＣＤ８及ＣＤ２５４种表型。差异无显著性（Ｐ＞０．０５）。在全部培养过程中，每组标本ＣＤ４／ＣＤ８始终大于１。３组效应细胞均显示较高的ＮＫ杀伤活性（Ｐ＞０．０５）。实体瘤组ＴＩＬ和非血性腹水组ＴＡＬ在５０∶１的效靶比时具有明显的抗ＡＴＣ特异性，而血性腹水组ＴＡＬ未显示这种特异性，经５１Ｃｒ检测的杀伤活性分别为３０２％～５１０％和１０８％～１５８％，差异有极显著性（Ｐ＜０．０１）。结论卵巢上皮性癌ＴＩＬ及其非血性腹水组ＴＡＬ具有相似的生物学特性。     

IL-2基因转移对卵巢癌细胞系SKOV3粘附性的影响

目的：研究ＩＬ－２基因转移对卵巢癌ＳＫＯＶ３细胞系粘附性的影响。方法：细胞对塑料基质、细胞基底膜成分的粘附实验,流式细胞术测定ＣＤ４４Ｈ的表达。结果：ＥＤＴＡ介导的细胞分离实验表明,ＳＫＯＶ３／ＩＬ－２细胞对塑料基质的粘附能力明显下降（Ｐ＜０．０１）;对基质及基底膜成分的粘附实验表明,ＳＫＯＶ３／ＩＬ－２细胞对Ⅳ型胶原和ｍａｔｒｉｇｅｌ的粘附能力下降,但对ＬＮ、ＦＮ的粘附能力无明显改变;粘附分子ＣＤ４４Ｈ的表达：ＳＫＯＶ３、ＳＫＯＶ３／Ｎｅｏ、ＳＫＯＶ３／ＩＬ－２组细胞粘附分子ＣＤ４４Ｈ阳性细胞百分率分别为７６．２％、６６．７％和３７．８％,ＳＫＯＶ３／ＩＬ－２组明显降低（Ｐ＜０．００１）。结论：ＩＬ－２基因修饰可使卵巢癌细胞系ＳＫＯＶ３粘附能力下降。     

分娩对产妇和新生儿免疫状况的影响

应用流式细胞技术检测了共４０例正常孕妇分娩前后和新生儿脐血的白细胞和淋巴细胞亚群。其中阴道分娩组２０例，造反性剖宫产组２０例。结果：分娩前后母体白 数和中性粒细胞，ＮＫ细胞活性以及ＣＤ８、ＣＤ１９亚群均相关不显著，而产后母血ＣＤ４业群升高，ＣＤ３、ＣＤ４／ＣＤ８亦升高，剖宫产或阴道分得母体和新生儿淋巴细胞亚嫩相差不显著，但阴道分娩新生儿的白细胞总数，中性粒细胞比例、单核细胞和ＮＫ细胞显著升高。提示     

卵巢功能早衰患者抗卵巢抗体及细胞免疫功能的测定

目的：探讨卵巢功能早衰（ＰＯＦ）患者细胞免疫功能的变化及其与抗卵巢抗体（ＡＯＡｂ）之间的关系。方法：检测３０例正常妇女（对照组）和３０例ＰＯＦ患者（ＰＯＦ组）的血清ＡＯＡｂ、外周血Ｔ淋巴细胞亚群及对卵巢抗原的白细胞促凝血活性（ＬＰＣＡ）。结果：对照组血清ＡＯＡｂ水平为１．３９±０．７２ｋＵ／Ｌ，ＰＯＦ组血清ＡＯＡｂ水平为６．８０±１．９１ｋＵ／Ｌ，两者比较，差异有极显著性（Ｐ＜０．０１）。与对照组比较，ＰＯＦ组ＣＤ＋３、ＣＤ＋４细胞百分率（分别为６５．４２±５．３１％和４４．７９±５．９０％）明显升高，ＣＤ＋８细胞百分率（２５．６３±４．２６％）明显降低，ＣＤ４＋／ＣＤ＋８比值（１．６６±０．２７）增加（Ｐ＜０．０１）。ＣＤ＋４／ＣＤ＋８比值升高者的ＡＯＡｂ阳性率（８５．７％，１８／２１），明显高于ＣＤ＋４／ＣＤ＋８比值正常者（３／９，Ｐ＜０．０１）。ＡＯＢｂ阳性的ＰＯＦ患者ＬＰＣＡ水平上升，且与ＡＯＡｂ之间有非常显著的相关性（χ２＝８．３７８，Ｐ＜０．０１）。结论：ＰＯＦ患者对卵巢抗原同时产生细胞免疫和体液免疫反应，ＰＯＦ的发病可能与免疫因素有关。     

输精管结扎家兔外周血淋巴细胞丝裂原反应性、IL－2及巨噬细胞IL－1活性的动态研究

体重２．５～３．０ｋｇ的日本大耳白雄兔２８只，分为输精管结扎组（ＶＧ，１８只）和假手术对照组（ＳＯＧ，１０只）。ＶＧ行双侧输精管结扎手术，ＳＯＧ只行双侧输精管暴露手术，术后第４、８、１２、１８、２２月检测外周血淋巴细胞对丝裂原反应性、ＩＬ—２和巨噬细胞ＩＬ－１活性。结果表明：１．ＣｏｎＡ和ＰＨＡ诱导的淋巴细胞丝裂原反应性，术后第８月ＶＧ的３Ｈ—ＴｄＲ掺入量均明显低于明Ｇ（Ｐ＜０．０１），而术后第４、１２、１８、２２月的测定结果与ＳＯＧ比较均无差异（Ｐ＞０．０５）。２．ＩＬ－２活性也以术后第８月为最低，与ＳＯＧ比较差异显著（Ｐ＜０．０１），１２月后恢复正常。３．ＣｏｎＡ诱导的淋巴细胞丝裂原反应性和ＩＬ－２活性间呈有意义的正相关关系（ｒ＝０．６６１，Ｐ＜０．００１）。４．ＩＬ－１活性，ＶＧ第８月显著地高于ＳＯＧ第８月（Ｐ＜０．０５），其它各月检测结果两组比较无明显差异。     

卵巢癌独特型疫苗免疫接种方案的探讨

目的：探讨卵巢癌抗独特型抗体（６Ｂ１１ ）疫苗免疫接种的理想方案。方法：用６Ｂ１１ 免疫ＢｃＦ１ 小鼠,观察基础免疫和加强免疫诱导的免疫应答情况,探讨加强免疫间隔时间、剂量及免疫途径对诱导免疫应答的影响,基础免疫为６Ｂ１１ １００μｇ—ＫＬＨ＋ ＣＦＡ,加强免疫为６Ｂ１１—ＫＬＨ＋ ＩＦＡ（或ＰＢＳ）,免疫部位为小鼠尾根及足底皮下或腹腔。观察指标：体液免疫为免疫鼠血清中抗原特异结合性抗独特型抗体（Ａｂ３ ）滴度,细胞免疫为免疫鼠脾脏淋巴细胞ＣＤ４＋ 、ＣＤ８＋ 亚群的变化。结果：（１）６Ｂ１１ 基础免疫后,Ａｂ３ 阳性率为８０．００％ ,Ａｂ３ 滴度高峰在第１４～２１天（１：３２０）,ＣＤ４＋ 亚群增加,ＣＤ＋８ 亚群变化不明显;（２）间隔４ 周加强免疫诱导的Ａｂ３ 滴度较２ 周者高,ＣＤ４＋ 亚群增加明显;６Ｂ１１５０μｇ 加强免疫诱导的免疫应答强于３０、１５μｇ;皮下途径加强免疫诱导的免疫应答略强于腹腔注射;（３）６Ｂ１１３ 次免疫后,Ａｂ３ 产生快（第３天１：３２０）,滴度高（最高１：６４０）,持续时间长（第４９天为１：４０）,ＣＤ＋４ ／ＣＤ８＋ 比值明显增加。结论：卵巢癌抗独特型抗体６Ｂ１１可作为肿瘤疫苗诱导ＢｃＦ１小鼠?     

稳定期系统性红斑狼疮孕妇外周血淋巴细胞亚群及白细胞介素-2受体的变化

目的：探讨系统性红斑狼疮（ＳＬＥ）孕妇在ＳＬＥ稳定期外周血中的Ｔ淋巴细胞亚群、自然杀伤细胞（ＮＫ细胞）及可溶性血清白细胞介素－２受体（ＳＩＬ－２Ｒ）的改变。方法：采用流式细胞仪对１４例ＳＬＥ稳定期（仅服用小剂量激素）的患者妊娠时（ＳＬＥ＋ＮＰ组）的Ｔ细胞亚群和ＮＫ细胞进行检测，同时用固相酶联反应法（ＥＬＩＳＡ）检测其ＳＩＬ－２Ｒ。并以１８例稳定期ＳＬＥ未孕妇女（ＳＬＥ组）、２０例正常未孕妇女（ＮＮＰ组）和２０例正常孕妇（ＮＰ组）作对照。结果：ＳＬＥ＋ＮＰ组的辅助性－诱导性Ｔ细胞（ＣＤ４＋）细胞数量较其他３组有明显下降（Ｐ＜０．０１）；ＣＤ４＋／细胞毒性－抑制性Ｔ细胞（ＣＤ８＋）值，ＳＬＥ＋ＮＰ组较ＳＬＥ组和ＮＮＰ组有显著下降（Ｐ＜０．０１），ＮＰ组也有下降，ＳＬＥ＋ＮＰ组和ＮＰ组之间差异无显著性（Ｐ＞０．０５）。ＮＫ细胞数在４组间差异无显著性（Ｐ＞０．０５）；ＳＬＥ＋ＮＰ组ＳＩＬ－２Ｒ有明显增高（Ｐ＜０．０１），其他３组变化不显著（Ｐ＞０．０５）。结论：ＳＩＬ－２Ｒ和ＣＤ４＋细胞数量变化可能对判断稳定期ＳＬＥ孕妇病情进展有重要作用     

Longitudinal study of CD4+ cell counts in HIV-negative pregnant patients

Objective.?To evaluate the absolute CD4⁺, CD8⁺, and lymphocyte cell counts and percentages from the first trimester through 6–12 weeks post-delivery in normal human immunodeficiency virus (HIV)-negative pregnant patients.

Methods.?A longitudinal laboratory analysis was performed during pregnancy that involved 51 HIV-negative subjects with blood analysis obtained in all trimesters, at delivery, and 6–12 weeks post-delivery. Twenty-five HIV-negative non-pregnant controls were also evaluated. Blood was analysed for absolute CD4⁺, CD8⁺, and lymphocyte cell counts and percentages. Means, standard deviations, trends, and differences were examined.

Results.?The mean white blood cell (WBC) count is elevated above the non-pregnant state and this parameter increases through the pregnancy up to and including parturition. The mean absolute lymphocyte cell count, lymphocyte percentage, and absolute CD4⁺ cell count are significantly lower during pregnancy and the progression through pregnancy appears U-shaped. The mean absolute CD8⁺ cell count is not significantly different. The CD4⁺ and CD8⁺ percentages are higher during pregnancy and this elevation persists into the 6–12 week post-delivery time period. A 3-digit drop in CD4⁺ percentage is common during pregnancy between blood draws; whereas, a 30% decrease or more in absolute CD4⁺ cell count is rare.

Conclusions.?By longitudinal analysis, pregnancy appears to significantly elevate the mean values of the WBC count, CD4⁺ percentage, and CD8⁺ percentage, but significantly decreases the absolute lymphocyte count, lymphocyte percentage, and absolute CD4⁺ cell count when compared to non-pregnant controls. The mean absolute CD8⁺ cell count appears to be unaffected.     

Sertoli cell maturation in men with azoospermia of different etiologies

OBJECTIVE: To evaluate the involvement of Sertoli cell in different spermatogenic disorders. DESIGN: Retrospective case-control study. SETTING: Teaching hospital. PATIENT(S): Azoospermic men who underwent testicular biopsy for sperm recovery in preparation for intracytoplasmic sperm injection. INTERVENTION(S): Testicular biopsy evaluation by quantitative immunohistochemistry for the immature Sertoli cell markers anti-Müllerian hormone and cytokeratin 18 (CK-18). MAIN OUTCOME MEASURE(S): Relative area of immature Sertoli cells in testes with focal spermatogenesis, spermatocyte maturation arrest, or normal spermatogenesis. RESULT(S): The relative area occupied by immature Sertoli cells, as revealed by anti-Müllerian hormone and CK-18 expression, was highest in the 11 men with focal spermatogenesis. In the group representing normal spermatogenesis (obstructive azoospermia, 6 men) and in the group characterized by spermatocyte maturation arrest (6 men), the areas occupied by anti-Müllerian hormone- and CK-18-positive cells were minimal. CONCLUSION(S): Different etiologies underlie the spermatogenic disorders reported in this study. In focal spermatogenesis with high anti-Müllerian hormone and CK-18 expression, the spermatogenic impairment is associated with the presence of immature Sertoli cells. The detection of normal mature Sertoli cells in the spermatocyte maturation arrest group indicates that the spermatogenic defect that is accompanied by an impairment of meiosis is intrinsic to the germ line without affecting Sertoli cell differentiation.     

Pelvic inflammation induced by diagnostic laparoscopy in baboons

Objective: To test the hypothesis that diagnostic laparoscopy can cause pelviperitoneal inflammation.

Design: Retrospective analysis of data collected during a prospective controlled study in baboons.

Setting: An academic research environment.

Animal(s): Samples were collected during laparoscopies in female baboons at the Institute of Primate Research, Kenya.

Intervention(s): In the first part of the study, 44 laparoscopies were performed in 16 baboons (5 with a normal pelvis, 11 with endometriosis) during the luteal phase, with a time interval of 1 month. In the second part of the study, 53 laparoscopies were performed in 15 baboons (6 with a normal pelvis, 9 with endometriosis) during the late follicular and luteal phases of one cycle, with a median time of 3–4 days between each laparoscopy.

Main Outcome Measure(s): Peritoneal fluid (PF) was measured and analyzed for white blood cell (WBC) concentrations and, in the second part of the study, for the distribution of lymphocyte subsets (CD3, CD4, CD8, and CD20) and for the presence of cytokines transforming growth factor-β1, interleukin (IL)-6, and IL-10.

Result(s): In the first part of the study, PF volumes and WBC concentrations were comparable at the baseline and follow-up laparoscopies. In the second part of the study, PF obtained at the second laparoscopy showed a 10-fold increase in volume, a 3-fold increase in WBC concentration, a 10-fold increase in IL-6 concentration, and a 2-fold increase in transforming growth factor-β1 concentration when compared with PF obtained at the first laparoscopy. The PF subset of granulocytes and CD3-positive cells was higher and the PF subset of macrophages was lower at follow-up laparoscopies than at the baseline laparoscopy.

Conclusion(s): Diagnostic laparoscopy can cause peritoneal inflammation in baboons.     

妊娠中晚期外周血T淋巴细胞亚群和NK细胞的观察

目的 :检测孕妇外周血T淋巴细胞亚群和NK细胞的变化 ,探讨正常妊娠时母体的细胞免疫状态。方法 :健康孕妇 92例按孕周分为 3组 :中孕组 (孕周 13～ 2 7+ 6周 )、晚孕未足月组 (孕周 2 8～ 36 + 6周 )和足月组 (孕周 37～ 4 1+ 6周 ) ;另取同期健康未孕生育年龄妇女 2 0例作对照组。用流式细胞仪检测其外周血T淋巴细胞亚群和NK细胞的相对数 ,结合外周血白细胞计数计算其绝对数。结果 :正常孕妇外周血白细胞总数显著增加 ,其中粒细胞百分数和绝对数均显著增加 ,单核细胞绝对数增加 ,淋巴细胞百分数和绝对数均显著减少 ;CD3+ 细胞百分数显著增加 ,CD4 + 细胞百分数和绝对数均显著减少 ,CD4 + /CD8+ 比值显著下降 ,CD8+ 细胞差异无显著性 ;NK细胞百分数和绝对数均显著减少。随着孕周进展 ,CD4 + 细胞百分数和绝对数均逐渐减少 ,CD4 + /CD8+ 比值逐渐下降 ,中孕组与晚孕未足月组比较 ,差异有显著性 (P <0 .0 5 )。结论 :妊娠期母体细胞免疫功能处于免疫抑制状态 ;随着妊娠进展 ,这种抑制有一定程度的下降。     

CD10 expression in pure stromal and sex cord-stromal tumors of the ovary: an immunohistochemical analysis of 101 cases.

CD10 has been recently advocated as a good immunohistochemical marker for endometrial stromal tumors. Metastatic endometrial stromal tumors to the ovary and primary endometrioid stromal sarcomas may show overlapping histological features with pure stromal and sex cord-stromal tumors (SCSTs). We investigated CD10 expression in a large series of pure stromal and SCSTs of the ovary to ascertain whether CD10 may aid in this differential diagnosis. Archival material from 11 fibromas, 10 thecomas, 10 sclerosing stromal tumors (SSTs), 10 adult granulosa cell tumors (AGCTs), 4 luteinized AGCTs, 9 juvenile granulosa cell tumors (JGCTs), 9 Sertoli cell tumors, 9 Sertoli-Leydig cell tumors, 11 sex cord tumors with annular tubules, 10 steroid cell tumors (StCTs), and 8 fibrosarcomas of the ovary were immunostained for CD10. The percentage of cells stained (<5%, 5%-39%, 40%-75%, and >75%) and intensity of staining (1+, 2+, 3+) were evaluated. CD10 was expressed in 7 of 10 thecomas (4 with 5%-75% and mostly 1+), 9 of 10 SSTs (7 with 5%-39% + cells, mostly 1+), 9 of 10 AGCTs (<5%-39%, four 1+, five 2+), 1 of 4 luteinized AGCTs (<5% and 1+), 8 of 9 JGCTs (mostly <5% to 39% and +1), 4 of 9 Sertoli cell tumors (either focal or >75% with variable intensity), 4 of 9 Sertoli-Leydig cell tumors (mostly <10% with variable staining), with the Leydig cells being positive in only 1 tumor (1+ and <5%), and 7 of 10 StCTs (4 tumors with more than 75% + cells, from 1+ to 3+). All fibromas, all but 1 fibrosarcoma (<5% and 1+), and all sex cord tumors with annular tubules were CD10 negative. CD10 expression was frequently seen in StCTs, SSTs, and thecomas of the ovary, although the latter 2 categories usually showed only faint immunoreactivity. In conclusion the frequency and intensity of CD10 immunoreactivity in pure stromal and sex cord-stromal ovarian tumors are low and contrast with the typical strong and diffuse immunostaining seen in endometrial stromal tumors; however, faint CD10 positivity is consistent with the diagnosis of ovarian SCST. Steroid cell tumors are often positive for CD10, but these tumors do not pose problems in differential diagnosis with endometrial stromal tumors. CD10 may play a useful role in aiding the differential between endometrial stromal tumors in the ovary and SCST and stromal tumors.     

大鼠睾丸热作用后各类生精细胞DNA分析

目的:探讨热作用后大鼠睾丸各类生精细胞DNA变化和生精功能的改变。方法:雄性Sprague-Dawley大鼠80只,随机分热处理组(43℃,30min)和对照组(22℃,30min),热处理组按热处理后0.5d、1d、3d、6d、10d、25d、35d和50d随机分成8个亚组(n=6),每亚组相应设立对照组(n=4)。应用流式细胞仪,对各组大鼠睾丸各类生精细胞DNA含量进行检测和分析。结果:与对照组相比较,热作用后0.5-35d组4C(初级精母细胞)细胞群和6-50d组1C(精子细胞和精子)细胞群的比例显著降低(P<0.05),3-35d组2C(精原细胞和次级精母细胞)细胞群比例显著升高(P<0.05)。8个实验组4C∶2C和3-35d组1C∶2C均显著低于对照组(P<0.05),1d组1C∶4C显著高于对照组(P<0.05)。结论:热作用后首先引起初级精母细胞数量显著下降,其次为精子细胞及精子。热作用使生精过程多个环节效率降低,流式细胞术是一种研究热作用引起生精功能变化的有效方法,有助于分析各类生精细胞在热损伤后的DNA变化。     

Pregnancy-associated changes in peripheral blood lymphocyte subpopulations in normal Kuwaiti women.

It has recently been reported that healthy pregnancy is associated with systemic immunosuppression. The aim of this study was to evaluate the numbers and distribution of lymphocyte subpopulations in normal, healthy pregnant Kuwaiti women. Thirty-four healthy normotensive women in the 3rd trimester of pregnancy were studied using flow cytometry to define lymphocyte subpopulations and were compared with 16 non-pregnant women. A decrease in the absolute numbers of lymphocytes was observed affecting T cells (CD3+, CD4+, CD8+), B cells (CD19+), and natural killer cells (CD16+/CD56+). When analyzed as a percentage of the total lymphocyte population, there was a significant decrease in B cells and an increase in CD4+ T cells. The T cell population revealed increased expression of CD25 on CD4+ and CD8+ cells, of HLA-DR on CD8+ cells, and of CD54 on CD4+ T cells. The reduced number of lymphocytes suggests that Kuwaiti females may be immunosuppressed in the 3rd trimester of pregnancy. The presence of activated CD4+ T cells could indicate the expression of a regulatory suppressor T cell population, as Treg cells are CD4+CD25+, and suppressor T cells are thought to be CD8+. Future work is required to explore the significance of these T cell populations in pregnancy.     

Regulatory T cells vary over bleeding segments in asthmatic and non-asthmatic women

Sex hormones may play an important role in observed gender differences in asthma incidence and severity. Regulatory T cells (Treg cells) are presumed to be involved in asthma and may vary with hormone levels. To investigate the effects of sex hormones on levels of Treg cells (percentage of CD4+CD25+Foxp3+ lymphocytes that are CD127-), a cohort of 13 women (6 with and 7 without an asthma diagnosis) had blood drawn multiple times over the course of a bleeding segment (bleeding interval plus the following bleeding-free interval) and collected urine samples daily for measurement of estrogen (estrone E1C) and progesterone (pregnanediol-glucuronide PDG) metabolites. The samples from non-asthmatic women indicated no association between bleeding segment day and Treg cells. Asthmatic women showed a 3% increase in Treg cell percentage with each successive day over the bleeding segment. Among non-asthmatic women, Treg cell percentages were not associated with PDG levels on the same day, or 1, 2 or 3 days before Treg cell measurement. E1C was positively correlated with the Treg cell percentage measured only on the same day - a 5% increase in E1C was associated with a 1.4% increase in Treg cell percentage. Among asthmatic women, only E1C was associated with Treg cell percentages after adjusting for PDG on the same day and 1 and 2 days before Treg cell measurement. A 5% increase in E1C was associated with a 2.3% increase in Treg cell percentage. A larger study of contiguous cycles to better determine within-woman cyclicity of the observed patterns is needed.     

Activating T regulatory cells for tolerance in early pregnancy — the contribution of seminal fluid

A state of active tolerance mediated by T regulatory (Treg) cells must be functional from the time of embryo implantation to prevent the conceptus from maternal immune attack. Male seminal fluid and ovarian steroid hormones are implicated in regulating the size and suppressive function of the Treg cell pool during the peri-implantation phase of early pregnancy. Evidence that antigens and cytokine signals in seminal fluid regulate the maternal immune response includes the following: (1) the Treg cell-inducing cytokine TGFβ and male alloantigens are present in seminal fluid; (2) seminal fluid delivery at coitus is sufficient to induce a state of active immune tolerance to paternal alloantigen, even in the absence of conceptus tissue; (3) female dendritic cells can cross-present seminal fluid antigens to activate both CD8⁺ and CD4⁺ T cells, and (4) mating events deficient in either sperm or seminal plasma result in diminished CD4⁺ CD25⁺ Foxp3⁺ Treg cell populations at the time of embryo implantation. Ongoing studies indicate that the cytokine environment during priming to male seminal fluid antigens influences the phenotype of responding T cells, and impacts fetal survival in later gestation. Collectively, these observations implicate factors in the peri-conceptual environment of both male and female origin as important determinants of maternal immune tolerance. Defining the mechanisms controlling tolerance induction will be helpful for developing new therapies for immune-mediated pathologies of pregnancy such as miscarriage and pre-eclampsia.     

Experimental testicular teratoma promotes formation of humoral immune responses in the host testis

The testis is an immunologically privileged site. Very little is known about the factors regulating formation of immune responses elicited by a neoplasm in the testis. We have studied the immune response of the host testis against experimental testicular teratoma in mouse by localizing adhesion molecules (CD106, CD54, CD49d/CD29, CD44, CD18, CD8 and CD4), cytokines (IL-2, IL-4, IL-6, IL-10 and IL-12), T-cell costimulators (CD80, CD86) and the lipid antigen presenting molecule CD1d in the testis of 129/SvJ mice with and without experimental testicular teratoma. The testicular teratomas were induced by grafting male gonadal ridges from 12-day-old 129/SvJ mouse fetuses into testes of adult mice from the same strain. The tumors cultured intratesticularly for 2, 3, 4 and 8 weeks (three animals per time point) were used for immunocytochemistry. CD1d was detected in Sertoli cells and in some degenerated tubules of the host testis surrounding the graft. In the tumor, CD1d was detected in glandular epithelia, smooth muscle and in thin fibers of neural origin. IL-2 was observed in some blood vessels of the host testis and of the tumor and in occasional cell infiltrates around these vessels. Some tubular structures of the tumor were also positive for IL-2. IL-6 was detected in Sertoli cells of the normal testis and in Sertoli cells and in solitaryinterstitial cells as well as in the walls of some blood vessels of the host testis. The reaction for IL-6 was more prominent in the tubules apparently damaged by the growing tumor. In the tumor IL-6 was detected in epithelial structures, muscle cells, in thin fibers of neural origin and in some blood vessels. IL-10 was detected in individual cells in the interstitium and in degenerating tubules of the host testis. In the tumor the epithelial structures were positive for IL-10. The interstitium of the host testis was positive for CD106 and the embryonic testicular cords in the graft were also positive, but the tumor was negative. CD44 and CD18 were observed in some blood vessels and in degenerated tubules of the host testis. In the tumor CD44 and CD18 were occasionally observed in cartilage and in epithelial structures. The results of the present study suggest that cytokine microenvironment in the testis containing neoplastic tissue promotes activation of humoral immune responses. In addition, as the damaged seminiferous tubules expressed increased amounts of two cytokines promoting humoral immune responses, IL-6 and IL-10, it is possible that also in other conditions with damage to the tubules, humoral immune responses predominate.