The role of cytotoxic T cells in IgG4-related dacryoadenitis and sialadenitis,the so-called Mikulicz's disease

Abstract

Objectives. Immunoglobulin (Ig) G4-related dacryoadenitis and sialadenitis, the so-called Mikulicz's disease (MD), is a chronic inflammatory disease. However, little is known about its pathogenesis and pathological condition. In the present study, we used immunohistological techniques to compare the roles of cytotoxic T lymphocytes (CTLs) in MD and primary Sjogren's syndrome (SS). We examined the state of CTLs [cytotoxic granule-positive rate and programmed death-1 (PD-1) expression rate] in the salivary glands.

Methods. The study samples comprised 12 submaxillary glands from untreated MD patients and 12 labial glands from SS patients. We performed immunofluorescence and multicolor immunofluorescence to stain CD8, perforin (PRF), granzyme B (GZMB), and PD-1. We measured the total number of CTLs as well as the PRF⁺CTLs, GZMB⁺CTLs, and PD-1⁺CTLs.

Results. We found that the degree of infiltration of CTLs was equal in MD and SS, but the rate of CTLs with cytotoxic granules, especially PRF, in MD was less than in SS. In addition, the frequency of PD-1⁺CTLs in MD was higher than that in SS.

Conclusions. Cytotoxic granule-positive CTLs were in the minority in MD salivary glands, and this regulation might relate to PD-1 signals like the state of exhaustion and anergy.     

穿孔素和颗粒酶B在哮喘大鼠肺组织中的表达及重组人生长激素的干预作用

目的：探讨哮喘大鼠肺组织中穿孔素（PFP）、颗粒酶B（GzmB）的表达变化及重组人生长激素（rhGH）的干预作用。方法：30只雄性Sprague-Dawley大鼠随机分为正常对照组、哮喘模型组及rhGH干预组。通过苏木精-伊红染色观察卵蛋白激发作用及rhGH干预后哮喘大鼠气道的病理变化。TUNEL原位凋亡检测支气管上皮细胞凋亡,RT-PCR方法检测肺组织中PFP及GzmB mRNA的表达。结果：哮喘组支气管上皮细胞凋亡指数明显增高,而rhGH干预组的凋亡指数则明显低于哮喘组（P<0.05）;PFP和GzmB mRNA在对照组中呈低表达;在哮喘组的表达明显强于对照组（P<0.05）;rhGH进行干预后,PFP和GzmB mRNA表达明显低于哮喘组（0.48±0.08 vs 0.63±0.08;0.44±0.13 vs 0.71±0.15;均P<0.05）。PFP和GzmB mRNA表达与支气管上皮细胞凋亡率呈正相关（r分别为 0.800 和 0.806,P<0.05）。结论：PFP和GzmB参与了哮喘发病过程中的重要环节;rhGH可能通过降低PFP和 GzmB的表达抑制支气管上皮细胞的凋亡从而抑制气道重塑。     

RhIL-21对NK-92MI细胞生物学活性的影响

目的探讨rhIL-21对NK-92MI细胞免疫功能的影响。方法以不同浓度(25～100ng/ml)的rhIL-21培养NK-92MI细胞24～72h,观察NK-92MI细胞的增殖。以50ng/ml的rhIL-21处理NK-92MI不同时间后,FACS检测NK-92MI细胞的凋亡,NK-92MI细胞表面NKG2D受体及胞内颗粒酶-B蛋白的表达;细胞杀伤试剂盒检测NK-92MI细胞对靶细胞K-562的细胞毒效应;RT-PCR检测NK-92MI受体NKG2D,效应分子颗粒酶-B、穿孔素及细胞因子IFN-γ基因mRNA的表达;ELISA检测其分泌IFN-γ的水平。结果 RhIL-21虽能抑制NK-92 MI细胞的增殖(P<0.05),但不会促进细胞的凋亡(P<0.05)。RhIL-21能促进NK-92MI细胞穿孔素、IFN-γ、颗粒酶-B、NKG2D受体基因及相应蛋白质的表达上调(P<0.05)。rhIL-21预处理组NK-92MI对K-562细胞的细胞毒效应也明显增强(P<0.05)。结论 RhIL-21能增强NK-92 MI细胞的细胞毒效应,IL-21在肿瘤的免疫治疗中有潜在临床应用价值。     

Differential Expression of Perforin in Cytotoxic Lymphocyte in HIV/AIDS Patients of China

Cytotoxic lymphocytes are critical in the control of HIV replication, it has been shown that perforin is the key effector of killing machinery for CTLs and NK cells, so we investigated the circulating levels of perforin in CD8⁺T cells and NK cells by flow cytometry intracellular stain in Chinese HIV infected individuals, its association with disease progression was analyzed. Our results showed that NK cells express perforin more efficiently than CD8⁺T cells, CD8⁺T cells expressed perforin higher than that of healthy controls, but NK cells expressed lower perforin than that of healthy controls, both were not correlated with disease progression. but significantly associated with their numbers, anti-retrovirus therapy had no evident effects on peforin expression in CD8⁺T cells, but enhanced perfrin expression in NK cells, perforin expression in CD8⁺T cells and CD16⁺NK cells correlate with CD4⁺T cell counts significantly in HAART-treated group. Therefore, different mechanisms may be involved in regulating peripheral perforin expression in different cell types.     

斑秃患者外周血白细胞介素35的表达及其对调节性T细胞的功能调控

目的:观察斑秃患者外周血白细胞介素35（IL-35）表达变化,评估IL-35对斑秃患者调节性T细胞（Treg）活性的调控。方法:收集2019年12月至2021年1月在山西省人民医院就诊的斑秃患者81例（斑秃组）和健康志愿者27例（对照组）,分离血清和外周血单个核细胞（PBMC）,酶联免疫吸附试验（ELISA）检测血清I...     

Rapidly progressive Lennert's lymphoma terminating in fulminant hepatic failure

A 65-year-old male with rapidly progressive Lennert's lymphoma terminating in fulminant hepatic failure is presented. Staging radiological studies revealed that he had cervical and mediastinal lymph node swellings and multiple nodular lesions in the spleen. Lymph node biopsy specimens showed the proliferation of epithelioid cells interspersed with large blastic lymphocytes. These lymphocytes were CD3+, CD45RO (UCHL-1)+, CD4-, CD8+, CD56-, CD30-, CD15-, T-cell intracellular antigen-1+, granzyme B+ and perforin+, suggestive of the cytotoxic T-cell lineage. Under the diagnosis of Lennert's lymphoma, he was treated with standard CHOP chemotherapy. After two courses of the chemotherapy, despite the decreased size of cervical lymph nodes, high-grade fever and constitutional symptoms appeared. As multiple low-density nodules were observed in the liver by computed tomography, needle biopsy was performed. The biopsy specimens showed the proliferation of CD3+, CD4- and CD8+ lymphoma cells. Thereafter, the liver function deteriorated rapidly, and disseminated intravascular coagulation emerged. He died of rapidly progressive hepatic failure. This case is another example demonstrating that at least some of the Lennert's lymphomas phenotypically correspond with cytotoxic T-cell lymphomas, as was previously suggested by us [Am. J. Surg. Pathol.24 (2000) 1627]. It should be also emphasized that Lennert's lymphomas containing cytotoxic proteins may have a fulminant clinical course, which cannot be rescued by the conventional chemotherapy.     

乳腺癌HIFU后腋窝淋巴结内淋巴细胞杀伤活性的变化

目的:探讨高强度聚焦超声(HIFU)治疗乳腺癌原发灶后同侧腋窝淋巴结中淋巴细胞的Fas配体(FasL)、颗粒酶B(GzB)、穿孔素(Pf)等细胞毒性分子表达的变化.方法:用SP免疫组化方法检测HIFU组23例和对照组25例患者腋窝淋巴结中淋巴细胞的FasL、GzB和Pf的表达.结果:HIFU组腋窝癌转移阴性和阳性淋巴结内Fasl、GzB、Pf阳性细胞数明显高于对照组(P＜0.01).结论:HIFU治疗乳腺癌原发灶后肿瘤引流淋巴结(TDLN)内具有杀伤活性的淋巴细胞增多,细胞免疫增强.     

慢性乙型肝炎病人肝组织穿孔素表达对乙型肝炎病毒复制及其蛋白分泌的影响

目的 探讨慢性乙型肝炎病人（以下简称慢乙肝）肝组织穿孔素表达对外周血乙肝病毒载量及肝脏内、外乙肝病毒蛋白分泌的影响。方法 对47例慢性乙肝病人作肝脏穿刺活组织检查，用免疫组织化学技术检测肝组织穿孔素的表达、乙肝病毒HBsAg和HBcAg的分泌，并同期检测病人外周血HBeAg的水平及HBV DNA载量。结果 37例肝组织穿孔素表达阳性，其中强阳性13例。肝组织穿孔素表达越强，外周血HBV DNA载量越低，二者间存在显著的负相关关系（x^2=7．902，P=0．019）；穿孔素与肝内HBcAg表达也存在显著负相关关系（x^2=7．403，P=0．025），但与HBsAg的表达水平无关（x^2=0．454，P=0．797）。在HBeAg阳性和阴性组之间，发现肝组织穿孔素的表达似乎与血清HBeAg水平的分泌无关（x^2=1．881，P=0．390）；而对31例HBeAg阳性病人以200S／CO为界进一步进行分析，发现穿孔素表达越强，HBeAg水平越低，但二者间尚未见显著统计学意义（x^2=5．283，P=0．071）。结论 慢性乙型肝炎病人肝组织穿孔素表达似可抑制乙肝病毒蛋白和病毒的分泌与产生，因此肝内穿孔素表达的水平可能反映机体免疫功能发挥的抗病毒程度，因而成为影响乙肝预后的一项重要指标。