几种反应性氧代谢物逆转剂免疫佐剂作用的比较

目的 分析比较硫普罗宁(TIP)、还原型谷胱甘肽(GSH)、二氢氯组胺(DHT)3种反应性氧代谢物(ROM)逆转剂抗白血病细胞免疫治疗中的增效作用.方法 在K562细胞、NK细胞的混合培养系中分别加入单核细胞和白细胞介素-2,然后分别加入TIP、GSH、DHT,观察ROM水平及K562细胞抑制率(KIR)的变化.结果 加入E/MO=10/2、10/5、10/10三种浓度的MO,ROM水平分别为(389.79±43.83)U/L,(456.74±42.77)U/L,(601.42±21.92)U/L,KIR分别为82.36%,81.36%,48.09%:加入TIP、GSH或DHT后,当E/MO=10/2时,ROM水平从(389.79±43.83)U/L,分别减至(-1.20±60.70)U/L、(-3.58±9.49)U/L和(50.21 4-22.4)U/L(P＜0.05),随着TIP、GSH或DHT浓度的增加ROM水平逐渐减少,KIR从82.53%分别升至96.09%、96.39%和94.64%(P＜0.05).结论 TIP、GSH逆转ROM的效应强于DHT,提高NK细胞对K562的抑制率,其效应强度与DHT相似,但毒副作用轻微,两者均可能成为更理想的抗白血病的免疫佐剂.     

CD4+CD25+T细胞的扩增方法与临床应用

CD4+CD25+T细胞是最重要的一类调节性T细胞(Tr).体内固有CD4+CD25+T细胞的自然扩增率极低,不能满足临床治疗的需要.通过采用FoxP3基因转染技术、阻断细胞活化信号、DC诱导、加入细胞因子等方法,对CD4+CD25+T细胞的数量和功能进行扩增,使其在器官移植、自身免疫性疾病和肿瘤免疫等领域具有广泛的临床应用前景.     

Dissecting the complexity of the memory T cell response

Memory immune responses are classically attributed to the reactivation of long-lived, antigen-specific T lymphocytes that persist in a quiescent state. Determining mechanisms for the generation of memory T cells and dissecting the functional nature of the memory T cell pool has been encumbered by an inability to distinguish recently activated effector T cells from memory T cells. We have established new activation and biochemical criteria that distinguish effector and memory T cells and have applied these criteria to follow memory generation from activated cells in vivo. We found that the resultant memory T cell pool is heterogeneous and consists of effector-like and resting memory-like subsets that differ in expression of the homing receptor, CD62L. We discuss these findings in the context of memory T cell heterogeneity identified in human and mouse systems. These results suggest that more than one type of previously activated T cell can mediate recall or memory immune responses and that elucidating the fundamental phenotypic and functional features of memory T cell subsets is therefore critical to deciphering the complex nature of the memory immune response.     

白术多糖对小鼠淋巴细胞功能的调节

研究了白术多糖ＰＡＭ体内及体外对小鼠脾淋巴细胞的调节作用。结果表明：白术多糖ＰＡＭ在一定的浓度范围内能单独激活或协同ＣｏｎＡ／ＰＨＡ促进正常小鼠淋巴细胞转化并能明显提高ＩＬ－２分泌的水平。ＰＡＭ对氢化可的松造成的免疫抑制小鼠淋巴细胞的增殖功能有恢复作用。同时还发现白术多糖ＰＡＭ对淋巴细胞的调节与β－肾上腺素受体激动剂异丙肾上腺素相关。     

NOD/SCID孕鼠淋巴细胞表型检测和NK细胞活性分析

目的观察NOD/SCID小鼠免疫状况和生育力特征,并分析NK细胞亚群对同基因交配组合NOD/SCID×NOD/SCID妊娠结局的影响。方法采用流式细胞术对未孕和孕13.5 d的NOD/SCID小鼠进行淋巴细胞表型分析,并系统地观察和比较NOD/SCID×NOD/SCID和BALB/c×BALB/c小鼠的生育力特征。分别采用多聚次黄苷酸-胞苷酸(polyinosinic-polycytidylic acid,poly I∶C)或抗asialoGM1单抗(anti-asialo GM1)刺激或抑制NK细胞活性,并分别观察这些因素对妊娠结局的影响。结果与对照组NOD/SCID小鼠相比,poly I∶C处理组NOD/SCID×NOD/SCID小鼠平均每窝产仔数增多,而注射抗asialo GM1单抗则使胚胎吸收率增高,进而平均每窝产仔数显著减少。结论在NOD/SCID小鼠孕期母-胎界面保持适当水平的NK细胞活性对妊娠结局有利。     

Diminished neo-antigen response to keyhole limpet hemocyanin (KLH) vaccines in patients after treatment with chemotherapy or hematopoietic cell transplantation

Relapse is the most common cause of treatment failure for advanced cancer, even those treated with autologous hematopoietic cell transplantation (HCT). Effective tumor-specific immunotherapy may decrease relapse, however, this will fail if the immune system is unable to respond. We developed a strategy to test immune responses with a single injection of the bona fide neo-antigen KLH. The model was first tested in 37 normal volunteers using three KLH vaccines: Intracel KLH, Biosyn KLH, and Biosyn KLH + adjuvant. Despite finding the immunogenic epitope conserved in both products, intact Intracel KLH induced a better response compared to a purified 350/390 kDA subunit of KLH contained in the Biosyn KLH product. Addition of a synthetic oil adjuvant (Montanide ISA51) restored the response to a single injection of Biosyn KLH. A quantitative readout measured by a KLH-specific cellular and humoral response with isotype switching 1 month after KLH vaccination was established. To test the integrity of the adaptive immune response in cancer patients, we vaccinated 14 patients post-HCT and 19 patients with advanced cancer with KLH vaccines that elicited a 100% response rate in normal volunteers. In marked contrast to normal subjects, both responses were significantly impaired up to 16 months after autologous HCT with an intermediate response in advanced cancer patients. KLH vaccines are safe and require only a single injection to test neo-antigen responses providing an optimal platform for definitive testing of strategies to improve diminished immune recovery after chemotherapy or post-HCT.     

CpG-ODN免疫学功能及其应用研究

近年来研究表明,细菌DNA与人工合成的寡核苷酸含有非甲基化的CpG基序,均能激活机体的免疫系统、诱导和增强天然免疫和获得性免疫反应,尤其显示出有效的T_(h1)型免疫佐剂效应,在某些感染性疾病、过敏性疾病和肿瘤等的防治中具有重要的应用前景。本文就近年来关于CpG-ODN的免疫学效应以及CpG-ODN在疫苗研制中的应用等问题进行综述。     

重组人IL-18在大肠杆菌中的表达及其抗肿瘤作用

目的：获取rhIL-18原核表达产物并研究其活性。方法：用本室构建的含基因重组表达载体PBV220-IL-18的大肠杆菌DHSot，经42℃热诱导表达和包涵体提取纯化后获取rhIL-18蛋白；采用ELISA试剂盒检测rhIL-18刺激PBMC分泌IFN-γ的活性及MTT法检测其对NK细胞杀伤K562细胞自然杀伤活性；同时用荷瘤小鼠模型检测其体内抗瘤功能。结果：诱导含重组表达载体PBV220-IL-18的大肠杆菌D145ct后，蛋白电泳显示出一条相对分子量（Mτ）为18000的蛋白条带；10μg rhIL-18蛋白体外刺激PBMC后，其分泌IFN-γ的能力与对照组相比提高了8倍，细胞毒性提高3倍；同时rhIL-18蛋白能明显抑制肿瘤生长和延长荷瘤鼠生存期。结论：获得了有免疫调节功能和抗肿瘤活性的rhIL-18蛋白。为今后IL-18重组产物的研制和开展肿瘤的生物治疗提供了实验依据。     

Vascular lesions in testes associated with male infertility in Cameroon

Summary Testicular biopsies in 40 of 41 infertile males with severe oligospermia in Cameroon presented massive subendothelial fibrinoid deposits in the small and medium sized vessels. Fibrinogen, complement and IgM were demonstrated in these deposits by immunofluorescence. Evidence strongly suggestive of parasitic testicular involvement was also observed in 2 cases.It is postulated that the fibrinoid deposits are the result of repeated formation and deposition of circulating immune complexes by reaction of antibodies with antigens. These antigens could be of various origins and in the cases described here they could be derived from living or dying parasites in the region. The accumulation and incorporation of the fibrinoid deposits may lead to vascular stenosis resulting in chronic ischaemia, tubular atrophy and fibrosis, and finally oligospermia.     

SARS患者急性期病情严重程度与康复期免疫功能的关系

目的考察SARS患者发病期病情轻重程度与康复期机体免疫功能受损的关系。方法将患者分为未使用呼吸机组（A）和使用过呼吸机组（B），通过回顾性分析SAILS患者住院期间和康复期的病例资料，比较两组患者肺部病灶阴影范围和吸收时间、WBC总数及其分类、康复期淋巴T细胞亚群与活化分子等。结果B组的肺部病灶范围在第2周内显著性大于A组，吸收时间也长于A组；A组的WBC总数，中性（N）、淋巴细胞（L）计数和百分数均在正常参考值范围，B组WBC总数、N计数与百分数高于A组，L百分数低于A组；第1次随访B组CD8^＋、CD8^＋／CD28^-、CD3^＋／HLA-DR^＋T细胞显著性高于A组，CD3^-／HLA—DR^＋细胞显著低于A组；第2次随访仅B组CD3^-／HIA—DR^＋细胞仍显著低于A组，其余免疫细胞无统计学差异。结论SAILS患者未使用呼吸机组较使用过呼吸机组肺部病理性损害小，免疫功能基本正常或受损程度很小。