Effect of Vasocation Intestinal Peptide on Immune Privilege of the Rat Testis

Objective To study the effect of vasocation intestinal peptide （VIP） on immune privilege of the rat testis. Methods The UU infected SD rats and Leydig cells were intervened by VIP, the secretion of TGF-β and the expression of FasL in rat Leydig cells were compared between VIP-intervened group and control group to test the effect of VIP on immune privilege of the rat testis in vitro and in vivo. Results In vitro, the secretion of TGF-β in Leydig cells could be increased by low dosage of VIP while inhibitited by high dosage of VIP; expression of FasL mRNA in Leydig cells could be decreased by VIP In vivo, increased expression of TGF-β mRNA and decreased FasL mRNA were observed in VIP group in 2-3 weeks after infected by UU. In addition, the apoptosis of Jurkat cells mediated by Leydig cells could be prevented by VIP Conclusion When Leydig cells or testis infected by UU, VIP could regulate the immune function of rat Leydig cells and participate in the regulation of immune privilege of testis through the regulation of TGF-β secretion and FasL expression pattern of Leydig cells.

Fas ligand expression in colon cancer:A possible mechanism of tumor immune privilege

AIM: To detect the expression of Fas ligand (FasL) in colon cancer tissues and cell lines and analyze the function of FasL-expressing colon cancer cells in inducing Fas-sensitive T lymphocyte apoptosis. METHODS: Ninety surgically resected colon cancer tissues and 15 hepatic metastasis specimens were investigatedby immunohistochemical method with normal colon mucosa and colon adenoma as control. The relationship between FasL expression and pathologic features was also analyzed.FasL expression of 4 colon cancer cell lines, SW620, Lovo, LS-174T and SW1116, were detected by Western blotting assay. The function of FasL expressed on colon cancer cells was determined by coculture assay with Jurkat T lymphocytes, the apoptotic rate of which was detectedby flow cytometry assay.RESULTS: Fifty-six (62.22%) cases of all the 90 colon cancer tissues and all (100%) the liver metastasis specimens expressed FasL, significantly higher than normal colon mucosa and colonic adenoma. Higher expression of FasL was found in more advanced stage of colon cancer and in cancer tissues with lymphatic or hepatic metastasis.All the colon cancer cell lines were found to express FasL.After coculture with the SW1116 cells for 24 h with an effector: target ratio 10:1, the rate of apoptosis of Jurkat cells rose from 1.9% to 21.0%.CONCLUSION: The expression of FasL is upregulated in colon cancer and the functionally expressed FasL can induce apoptosis of Fas-expressing T lymphocytes.

The effect of FasL gene transfer to islet cells on pancreatic islet allografts

OBJECTIVE: To investigate the effect of FasL gene transfer to islet cells on pancreatic islet allografts. METHODS: A recombinant and replication-deficient type-5 adenovirus encoding murine FasL (AdV- FasL) was constructed by the method of calcium phosphate precipitation. Pancreatic islets were infected with the recombinant adenovirus AdV-FasL, and transplanted into diabetic recipients. FasL expression was detected by RT-PCR and immunohistochemistry. The survival of allografts and the apoptosis of gene transferred islet allografts were analyzed. RESULTS: All animals receiving islet allograft alone returned to a diabetic state by several days (mean survival time 6.3±0.6 days). Compared with the control group, no delayed rejection and prolonged survival of allografts were observed in the group of FasL gene transfer. The rejection was accelerated and the allograft survival was shortened to 3.4±0.2 days (P<0.05). Pancreatic islets infected with AdV- FasL demonstrated positive staining of FasL at 24 h, with an increased intensity at 48 h, but not in AdV-5 infected or uninfected islets. TUNEL labeling of pancreatic islet allografts at 24, 48 h revealed apoptosis that was not in AdV-5 infected allografts. CONCLUSIONS: Though co-transplantation of FasL-expressing testicular cells can induce privilege of islet allografts and prolong allograft survival, direct expression of FasL on islet allografts infected with AdV-FasL may accelerate islets rejection by islet apoptosis and granulocyte infiltration.

Effects of Ureaplasma Urealyticum on Fas Ligand Expression in Rat Sertoli Cell

To investigate the effect of ureaplasma urealyticum (UU) on the expression of Fas ligand (FasL) on rat Sertoli cell Materials & Method Isolated rat Sertoli cells were infected by living UU, UU super- natants, inactivated UU, then Fluorescence Activated Cell Sorter and observed fluores- cence microscopy were used to assay for the FasL expression on the surface of Sertoli cells. Results UU infection could increase the expression of FasL in Sertoli cell. Conclusion The functional expression of FasL is related to the immune privilege and can give the immune regulation on the testis.

Loss of Anterior Chamber-Associated Immune Deviation during Normal Pregnancy in Primates

Purpose: We recently found that loss of anterior chamber-associated immune deviation was associated with normal pregnancy in rabbits. The purpose of this study is to further investigate whether the same events occurred in nonhuman primates. Methods: Mid-pregnant cynomolgus monkeys were randomly selected. Bovine serum albumin (BSA) was inoculated in anterior chamber of eyes of nonpregnant and mid-pregnant monkeys that were subsequently immunized with BSA in adjuvant. Delayed-type hypersensitivity (DTH) was assessed by skin challenge.Results: Non-pregnant monkeys of intracameral BSA proved able to acquire antigen-specific suppression of delayed-type hypersensitivity. By contrast, inoculation of BSA to anterior chamber of pregnant monkeys abolished the DTH-suppression effect. Conclusions: This is the first demonstration in primates that loss of anterior chamber-associated immune deviation occurred during normal pregnancy. The fluctuations of systemic hormone levels during normal pregnancy might influence

BTK抑制剂治疗原发免疫豁免部位大B细胞淋巴瘤的研究进展

原发免疫豁免部位大B细胞淋巴瘤(primary immune-privileged site large B-cell lymphoma,IP-DLBCLs)是世界卫生组织(WHO)淋巴样肿瘤分类第5版新的类别总称,指一组原发于免疫功能正常患者的免疫屏障之后部位的侵袭性B细胞淋巴瘤,起源于各自的解剖结构(如血脑、血网膜和血睾丸屏障)和各自原发部位的免疫调节系统所形成的免疫庇护所,并具有相同的免疫表型和分子特征,目前包括原发性中枢神经系统大B细胞淋巴瘤(primary central nervous system lymphoma,PCNSL)、原发睾丸大B细胞淋巴瘤(primary testicular large B-cell lymphoma,PTL)和原发玻璃体视网膜大B细胞淋巴瘤(primary vitreoretinal large B-cell lymphoma,PVRL)。该类疾病预后相对较差,目前尚无标准的治疗方案。Toll样受体(TLR)信号(通过MYD88突变)和B细胞受体(BCR)信号(通过CD79B突变)通路介导的NF-κB激活是三者发病的核心机制。该共同属性为这一类疾病的治疗提供了通用的靶点。BTK(Bruton’s tyrosine kinase,BTK)是上述信号通路的中心分子。因此,BTK抑制剂可能是这类疾病合理的治疗药物选择。本文将就BTK抑制剂治疗原发免疫豁免部位大B细胞淋巴瘤的作用机制、临床研究、不良反应及耐药问题进行综述。

Mechanisms of testicular immune privilege

The testis exhibits a distinctive form of immune privilege to protect the germ cells from the host immuneattack. The property of testicular immune privilege was originally attributed to the blood-testis barrier in theseminiferous epithelium, which sequesters antigens. Recent studies have uncovered several levels of immune controlbesides the blood-testis barrier involved in the privilege of the testis, including the mechanisms of immune tolerance,reduced immune activation, localized active immunosuppression and antigen-specific immunoregulation. The somaticcells of the testis, especially Sertoli cells, play a key role in regulating the testicular immune privileged status. Theconstitutive expression of anti-inflammatory factors in the testis by somatic cells is essential for local immunosuppression.Growing evidence shows that androgens orchestrate the inhibition of proinflammatory factors and shift cytokinebalance toward a tolerogenic environment. Disruption of these protective mechanisms, which may be caused by trauma,infection and genetic factors, can lead to orchitis and infertility. This review article highlights the unique immuneenvironment of the testis, particularly focuses on the regulation of testicular immune privilege.

睾丸Sertoli细胞对共移植同种异体肾细胞的保护作用及受体性别的影响

目的探讨表达FasL的睾丸Sertoli细胞对不同性别受体大鼠中移植肾细胞的保护作用。方法用酶消化法制备Sertoli 细胞及肾细胞。流式细胞仪检测细胞表面FasL及Fas的表达。将约106个细胞(注入的细胞因分组不同而异,见1.2.3)注入异体肾包膜下，用SABC法测定肾细胞的存活状况，并以TUNEL法观察移植物中的淋巴细胞凋亡。结果移植后20d，用组织学分析移植细胞的存活率。单纯肾细胞移植，移植物无一例存活；混合细胞移植，移植物的存活率为87.5％。以抗FasL抗体处理过的Sertoli细胞与肾细胞共移植，肾细胞的存活率仅为30.0％，雌性受体移植物的存活率为77.8％。移植物中可见凋亡的淋巴细胞。结论同种异体移植中，Sertoli细胞对移植的肾细胞具有保护作用，其机制与Fas/FasL系统介导的淋巴细胞凋亡有关。

成人睾丸支持细胞的分离培养及其免疫豁免机制

目的:建立成人睾丸支持细胞的体外培养方法并探讨其免疫豁免机制。方法:依次用胰蛋白酶、胶原酶、透明质酸酶及脱氧核糖核酸酶消化制备成人睾丸支持细胞,以SABC染色法检测支持细胞上Fas-L和TGF-β1的表达。将其与成人脾细胞共同培养,用MTT比色法检测其对脾细胞增殖的抑制作用。结果:成人睾丸支持细胞占培养细胞总数的80%以上,活性可达90%。睾丸支持细胞上可表达Fas-L和TGF-β1,体外可抑制共培养的脾细胞增殖。结论:建立了培养成人睾丸支持细胞的方法,其免疫豁免机制可能与Fas-L和TGF-β1的表达有关。

斑秃免疫学发病机制研究进展

斑秃是一种毛囊的T细胞介导的自身免疫性疾病,毛囊免疫耐受被打破,黑素细胞相关蛋白激发Th1型免疫反应主要攻击生长期毛囊,引起骤然非瘢痕性毛发脱失。毛囊研究的便宜性和斑秃体外模型的成熟建立使斑秃免疫学研究在自身免疫性疾病的研究中占有优势地位。本文从免疫相关基因的易感性、自身抗原表位扩展、自身抗体的体内非致病性、T细胞相互作用与调节等方面对斑秃的免疫学发病机制进展作了回顾,以助于研究者对其有更好的理解。

溶脲脲原体感染对大鼠睾丸Sertoli细胞FasL表达的影响

溶脲脲原体（Ｕｒｅａｐｌａｓｍａ Ｕｒｅａｌｙｔｉｃｕｍ，ＵＵ）是泌尿生殖道感染的常见病原体，可导致睾丸明显的病理损伤，且与不育有关。本文以对数生长期的ＵＵ、热灭活ＵＵ和ＵＵ上清液体外感染或作用于大鼠的Ｓｅｒｔｏｌｉ细胞，观察Ｓｅｒｔｏｌｉ细胞表面 ＦａｓＬ表达的变化。实验证明，活ＵＵ、热灭活 ＵＵ和 ＵＵ上清感染后，Ｓｅｒｔｏｌｉ细胞表面 ＦａｓＬ表达均增加，其中以活ＵＵ感染的影响最为明显。提示睾丸组织的免疫豁免与其局部的ＦａｓＬ功能性表达有关；在感染时，Ｓｅｒｔｏｌｉ细胞通过上调ＦａｓＬ的表达以维持睾丸局部免疫豁免的保护机制。

超抗原SEB诱导的免疫耐受参与免疫赦免部位的应答反应

目的:探讨超抗原葡萄球菌肠毒素B(SEB)诱导的耐受性是否参与免疫赦免部位的应答反应。方法:以LEW大鼠作为受体,F344大鼠作为供体,进行角膜移植。将受体鼠随机分成5组,即在手术前7 d及移植后7 d,以球旁途径分别注射30μg/kg、60μg/kg、90μg/kg和120μg/kg的SEB组和注射生理盐水的阴性对照组。阳性对照组分别为移植后注射糖皮质激素(GC)、FK506、环孢素A((CsA)和白介素-1受体拮抗剂(IL-1 ra)组。镜下观察移植后30 d内角膜的浑浊、水肿和新生血管,用抗排斥反应指数记录移植片存活天数。采用NK1.1-PE荧光抗体进行组织染色,观察移植后不同时间受体鼠角膜片的炎症细胞浸润和受体鼠眼局部NK细胞的变化。结果:注射120μg/kg SEB的大鼠移植片比生理盐水对照组的存活天数延长了22 d。与FK506、CsA、IL-1ra和GC组相比也明显延长。120μg SEB/kg受体鼠的移植片排斥反应指数为3.42±2.18,明显低于对照组6.58±3.15(P<0.01)。其中水肿指数和新生血管指数明显降低。组织染色结果显示,SEB注射后NK细胞数量增加。结论:注射SEB能降低大鼠角膜移植的排斥反应,提示SEB诱导的耐受性参与了免疫赦免部位的应答反应。

免疫赦免在小鼠角膜移植排斥中的作用研究

目的:阐明同种异体小鼠角膜移植术后免疫排斥反应及免疫赦免的相关性。方法:建立小鼠原位角膜移植及同种异体小鼠角膜移植实验模型。观察原位移植与同种异体移植术后角膜植片发生排斥的情况,对比两种移植术后植片的存活率,了解小鼠角膜移植术后发生排斥反应与免疫赦免反应之间的关系。结果:小鼠原位角膜移植术后植片100%存活;同种异体小鼠角膜移植术后存活率为25%。结论:小鼠角膜移植术后免疫排斥并非绝对,免疫赦免在角膜移植术中发挥重要作用。

睾丸FasL^+Sertoli细胞的制备及功能测定

目的简化大鼠睾丸支持细胞分离培养方法,获取高成活率、高数量、高表达的Fas配体阳性支持细胞。方法取2-3周龄大小的Wistar雄性大鼠,应用胶原酶、胰蛋白酶及脱氧核糖核酸酶消化制备大鼠睾丸支持细胞,体外与活性淋巴细胞共同培养,了解其对淋巴细胞的杀伤作用。用不同方法进行形态学观察、鉴定,免疫组化检测Fas配体和卵泡刺激素受体的表达情况,进一步鉴定睾丸支持细胞。结果大鼠睾丸支持细胞的分离培养中,支持细胞存活率在90%以上,并有明显的Fas配体表达。支持细胞可杀伤与之共同培养的活性淋巴细胞。结论本法提高了支持细胞的获取量,获取的对活性淋巴细胞具有的杀伤作用的Fas配体阳性睾丸支持细胞可以作为联合移植的供体,发挥其局部免疫豁免作用。

细胞凋亡与眼的免疫赦免

眼内细胞构成性表达Fas分子的配体 (FasL)。FasL可以诱导入侵眼内的Fas+ 淋巴细胞发生凋亡。该机制具有双重作用 ,一是限制局部炎症的扩散 ;二是参与免疫偏离的建立。眼的免疫赦免除与被动的物理屏障和隔离机制有关外 ,还与多重的主动机制有关。这些机制的共同作用是免除眼组织发生免疫性炎症反应以维持眼器官的完整性。

碱烧伤对眼前房免疫赦免状态的削弱和破坏

目的观察碱烧伤后眼免疫赦免状态的改变。方法使用０．５ｍｏｌ／ＬＮａＯＨ在兔眼建立碱烧伤模型。通过胸腺细胞刺激反应检测碱烧伤后不同时间房水的免疫抑制水平。另外，观察了碱烧伤对前房相关免疫偏离（ＡＣＡＩＤ）的支持能力。结果碱烧伤后眼房水的正常免疫抑制效应显著下降，即使在碱烧伤后２个月。烧伤眼接种抗原后ＡＣＡＩＤ诱导失败。结论碱烧伤后角膜移植免疫排斥反应的高发率除与植床的高度血管化和炎症背景外。

破坏视网膜Muller细胞对眼免疫赦免的影响

目的探讨视网膜Muller细胞在眼免疫赦免诱导和维持中的作用。方法在Wistar大鼠和新西兰白兔的右眼玻璃体腔接种Muller细胞的特异性破坏剂L－α－氨基已二酸（L－α－AAA）和10g·L1牛血清白蛋白。不同时间分别摘除接种眼，进行透射电镜检查。动物模型建立1wk后，进行DTH的诱导和测量。结果玻璃体腔接种L－α－AAA4h，视网膜Muller细胞肿胀、电子密度降低；12h以上病变加重；48h以上病变减轻；72h恢复正常。玻璃体腔接种L－α－AAA和抗原组的动物DTH反应均呈阴性。非玻璃体腔抗原接种组动物均呈阳性反应。结论在短时间内、单一的破坏视网膜Muller细胞，并不能造成眼免疫赦免状态的削弱或破坏。眼免疫赦免是一多因素、多机制的免疫调节过程，各因素之间具有相互叠加和相互补偿的作用。

HSP70与FasL在子宫内膜异位症中的表达

目的 :探讨热休克蛋白 70 (HSP70 )和Fas配体 (FasL)在子宫内膜异位症(EM)发病中的作用。方法 :采用免疫组化链霉菌抗生物素蛋白 -过氧化物酶染色法 (S P法 )检测子宫内膜异位症 5 6例的异位内膜与在位内膜 (30例 )中HSP70和FasL蛋白的表达 ,并以正常子宫内膜为对照 (2 5例 )。结果 :异位内膜组织中HSP70与FasL均呈高表达 ,与正常内膜组差异有高度显著性 (P <0 .0 1) ,而且二者失去在正常内膜组织中表达的周期性变化。但在卵巢子宫内膜异位症 (OEM)与子宫腺肌症 (AM)的表达差异无显著性 (P>0 .0 5 )。结论 :异位内膜组织中HSP70和FasL蛋白均过度表达 。

论记者拒证权

记者拒证权是指在司法活动中,新闻记者拒绝作证提供消息来源的权利。其保护对象不涉及提供者而只针对记者。记者拒证权的目的是为了保护信息来源,而不是信息本身。拒证权是利益平衡的结果,是寻求案件真相向新闻自由作出的必要让步。拒证权的内容可分为四个方面:(1)拒绝公开信息来源的身份;(2)拒绝开示可能曝光提供者身份的信息内容;(3)拒绝接受询问;(4)拒绝接受搜查、扣押。中国在记者拒证权问题上应当采取渐进式立法。

外伤性眼内炎对眼免疫赦免状态的影响

目的研究外伤后眼内炎症对眼免疫赦免状态的影响。方法在Ｗｉｓｔａｒ大鼠和新西兰白兔建立外伤性眼内炎模型。将牛血清白蛋白分别接种于受伤眼和正常眼玻璃体腔。接受附加佐剂的牛血清白蛋白免疫方案１周后，评价其诱导玻璃体腔相关免疫偏离的能力，并观察受伤眼组织病理学改变。结果眼外伤后５～７天发生中度到重度炎症反应。常规免疫组动物均出现抗原特异性迟发型超敏反应（ＤＴＨ）阳性；单纯玻璃体腔抗原接种组动物均显示ＤＴＨ阴性；受伤眼玻璃体腔抗原接种组和受伤眼玻璃体抗原接种后对侧正常眼玻璃体抗原接种组均显示ＤＴＨ阳性。结论外伤性眼内炎导致受伤眼和正常眼免疫偏离诱导的失败。眼相关免疫偏离的消失可能参与了交感性眼炎的发病过程。