细胞免疫功能及辅助型T细胞因子在口腔扁平苔藓中的作用

目的 探讨细胞免疫功能及辅助型T细胞（Th）细胞因子在口腔扁平苔藓（OLP）中的作用。方法 以35例糜烂型（糜烂组）及29例网纹型OLP（网纹组）患者为对象,选取同期20例健康人为对照组,流式细胞术检测外周血中T细胞、B细胞、NK细胞和调节性T细胞亚群表达百分率。ELISA法检测外周血中TNF-α和INF-γ（Th1型细胞因子）,IL-4和IL-10（Th2型细胞因子）,IL-17、IL-23（Th17型细胞因子）含量;分离外周血单个核细胞,qRT-PCR检测上述因子mRNA的表达。结果 与健康组相比,OLP患者CD3+、CD4+ T细胞亚群比例（F=3.211和3.565,P<0.05）及CD4+/CD8+降低（F=3.430,P<0.05）,CD4+Foxp3+调节性T细胞亚群比例（F=3.370,P<0.05）及外周血中TNF-α、INF-γ、IL-4、IL-10、IL-17、IL-23含量增高（F=0.923、0.820、1.043、1.132、0.745和0.802,P<0.05）。与网纹组相比,糜烂组CD8+ T细胞亚群比例较低（t=2.450,P<0.05）;IL-4、IL-10蛋白（t=22.780和25.112,P<0.05）及mRNA较低（t=3.781和6.710,P<0.05）,IL-17、IL-23蛋白（t=15.765和19.307,P<0.05）及mRNA较高（t=4.022和8.569,P<0.05）。结论 口腔扁平苔藓患者存在细胞免疫紊乱及Th细胞因子异常,其中CD8+及Th17型细胞与糜烂型OLP发病有关,Th2型细胞与网纹型OLP发病有关。     

HIV-1 Env vaccine comprised of electroporated DNA and protein co-administered with Talabostat

Selection of potent yet low reactogenic adjuvants for protein immunization is important for HIV-1 vaccine development. Immunogenicity of electroporated DNA (HIV env) and recombinant gp120, administered with either QS-21 or the orally administered immunomodulator, Talabostat, was evaluated in BALB/c mice. Electroporation of low dose DNA elicited Th1 cytokines and anti-envelope antibodies. Immunization with gp120 protein alone with or without Talabostat elicited lower Th1 and Th2 cytokine levels but comparable anti-gp120 antibodies to QS-21-formulated protein. Boosting of DNA-primed mice with gp120/Talabostat induced similar anti-gp120 antibody titers and slightly higher levels of Th1 and Th2 cytokines relative to QS-21-formulated protein. Induction of CD8⁺ and CD4⁺ T cells and functional CTL activity was noted. These results highlight the potential use of orally administered Talabostat for efficient protein boosting of antibody and T-cell responses primed by DNA.     

Persistent antibody and T cell responses induced by HIV-1 DNA vaccine delivered by electroporation

Intramuscular needle injection of HIV-1 DNA vaccines typically elicits weak immune responses in immunized individuals. To improve such responses, the immunogenicity of a vaccine consisting of electroporated DNA followed by intramuscular protein boost was evaluated in rabbits and macaques. In macaques, electroporation of low dose DNA encoding HIV-1 env followed by gp120 protein elicited Th1 cytokines and functional CTL that persisted for over 1 year. In both macaques and rabbits, robust anti-envelope antibodies, elicited by electroporated DNA, were augmented by gp120 protein and such responses neutralized sensitive SHIV isolates. These findings highlight efficient priming of immune responses by electroporated DNA that in conjunction with protein boost may give rise to long-term immunity in immunized hosts.     

Increased liver temperature efficiently augments human cellular immune response: T-cell activation and possible monocyte translocation

Hyperthermia (HT), in combination with other conventional therapeutic modalities, has become a promising approach in cancer therapy. In addition to heat-induced apoptosis, an augmented immunological effect is considered to be a benefit of hyperthermic treatment over chemo- or radiotherapy. Here, we investigated the effect of regional HT targeting the liver on immune cells, especially T cells and antigen-presenting cells, which are important in recognizing and eliminating tumor cells and pathogens such as viruses. In healthy volunteers exposed to such regional HT, both CD4⁺ and CD8⁺ T cells that express an activation marker CD69 increased transiently at 1 h post-treatment, with a subsequent decrease to base levels at 6 h after the treatment. At 24 h post-treatment, the percentage of CD69-positive cells significantly increased again but only among CD8⁺ T cells. IFN-γ production from PHA-stimulated peripheral blood mononuclear cells was gradually and significantly increased in the 2 days following the heating procedure, peaking at 36 h post-treatment. Furthermore, we found marked increases in plasma levels of IL-1β and IL-6 starting at 24 h post-treatment. With regard to the number of each leukocyte subpopulation, a transient and dramatic decrease in the number of a subset of monocytes, CD14⁺ CD16⁻ cells, was observed at 1 h after the hyperthermic treatment, suggesting that the regional HT aimed at the liver may have influenced the extravasation of blood monocytes. No significant changes in T-cell activities or monocyte counts were observed in the volunteers exposed to heating of the lungs or the legs. These results suggest that heating of the liver may efficiently induce cellular immune responses to liver cancers.     

Human T lymphocyte responses against lung cancer induced by recombinant truncated mouse EGFR

The induction of active cellular responses against EGFR should be a promising approach for the treatment of those receptor-positive tumors. However, the immunity against EGFR is presumably difficult to elicit by vaccine based on self or syngeneic EGFR due to the immune tolerance acquired during the development in immune system. We proposed a model to break immune tolerance against self-EGFR through an altered immunogen source based on xenogeneic homologous EGFR. We have previously shown human EGFR as a xenoantigen could induce specific immune responses in mouse and cross-react with mouse EGFR, and resulted in therapeutic benefits for EGFR-positive mouse tumor. Here, we show a recombinant form of extracellular domain of mouse EGFR, in the presence of DCs, could activate human peripheral T cells to proliferate, secret IFN-γ, the induced responses could cross-react with human EGFR and kill autologous EGFR-positive lung cancer cells which could be blocked by anti-CD8 and anti-MHC class I antibody. There is no detectable cytotoxical activity against lung tissue, liver tissue and kidney tissue derived from paracancerous normal tissue. These observations suggest that antitumor immunity induced by the truncated mouse EGFR may be provoked in a cross-reaction between mouse EGFR and self-EGFR, and may provide insight into treatment of EGFR-positive tumors through induction of the autoimmune responses against EGFR.     

Induction of antigen-specific immunity by pH-sensitive carbonate apatite as a potent vaccine carrier

The ability of carbonate apatite (CO₃Ap) to enhance antigen-specific immunity was examined in vitro and in vivo to investigate its utility as a vaccine carrier. Murine bone marrow-derived dendritic cells took up ovalbumin (OVA) containing CO₃Ap more effectively than free OVA. Interestingly, mice immunized with OVA-containing CO₃Ap produced OVA-specific antibodies more effectively than mice immunized with free OVA. Furthermore, immunization of C57BL/6 mice with OVA-containing CO₃Ap induced the proliferation and antigen-specific production of IFN-γ by splenocytes more strongly than immunization with free OVA. Moreover, no significant differences were detected in the induction of delayed-type hypersensitivity responses, an immune reaction involving an antigen-specific, cell-mediated immune response between OVA-containing CO₃Ap and OVA-containing alumina salt (Alum), suggesting that CO₃Ap induced cell-mediated immune response to the same degree as Alum, which is commonly used for clinical applications. This study is the first to demonstrate the induction of antigen-specific immune responses in vivo by CO₃Ap.     

抵抗女性生殖道沙眼衣原体感染的免疫新策略

沙眼衣原体是引起沙眼和泌尿生殖道感染的主要病原体.据世界卫生组织2015年统计,全球每年约有1.3亿沙眼衣原体感染新发病例.研究表明CD4+Th1型细胞免疫应答在抵抗沙眼衣原体感染中发挥着重要作用.因此,研究者依照抗沙眼衣原体感染的免疫应答特点,构建出许多候选疫苗,但都没有成功地应用于临床.近年研究发现,生殖道黏膜组织...     

Cellular immune response to an engineered cell-based tumor vaccine at the vaccination site

The engineered expression of the immune co-stimulatory molecules CD80 and CD137L on the surface of a neuroblastoma cell line converts this tumor into a cell-based cancer vaccine. The mechanism by which this vaccine activates the immune system was investigated by capturing and analyzing immune cells responding to the vaccine cell line embedded in a collagen matrix and injected subcutaneously. The vaccine induced a significant increase in the number of activated CD62L(-) CCR7(-) CD49b(+) CD8 effector memory T cells captured in the matrix. Importantly, vaccine responsive cells could be detected in the vaccine matrix within a matter of days as demonstrated by IFN-gamma production. The substitution of unmodified tumor cells for the vaccine during serial vaccination resulted in a significant decrease in activated T cells present in the matrix, indicating that immune responses at the vaccine site are a dynamic process that must be propagated by continued co-stimulation.     

miRNA对T细胞分化与功能的调节作用

miRNA是一类长度为19~24 nt的内源性非编码小分子RNA,主要通过抑制mRNA的翻译或使其降解对靶基因实现转录后水平的调控。miRNA与T细胞的分化及功能密切相关,参与自身免疫性疾病、感染性疾病、肿瘤等多种病理过程的免疫调控。本文综述了近年来发现的miRNA在T细胞分化与功能调节中的作用,特别是其在抗感染与抗肿瘤免疫中的作用。     

鼠疫F1抗原和V抗原双组分候选疫苗的免疫学评价

目的通过由提取的鼠疫F1抗原和重组鼠疫V(rV)抗原组成的鼠疫候选疫苗免疫豚鼠,对其免疫效果进行评价。方法将豚鼠随机分成5个试验组,在免疫后不同时间点采血进行抗体检测、MTT法淋巴细胞增殖试验以及皮肤迟发型超敏反应(DTH)检测。结果抗体检测结果显示,双组分鼠疫候选疫苗能诱导较强的体液免疫应答;MTT细胞增殖结果显示,脾脏淋巴细胞特异性增殖不明显;中剂量组、高剂量组针对F1和rV抗原DTH阳转率均为100%。结论双组分鼠疫候选疫苗能诱导豚鼠体液免疫和细胞免疫应答,该疫苗有希望成为我国新一代鼠疫疫苗。     

凝结芽胞杆菌对免疫功能影响的实验研究

目的 研究凝结芽胞杆菌（TQ33）对实验动物免疫功能模型的影响。方法 以鸡红细胞混悬液对小鼠腹腔注射,观察TQ33对小鼠腹腔巨噬细胞吞噬功能的影响;制备绵羊红细胞（SRBC）,观察血球凝集程度,测定血清溶血素;以靶细胞（YAC-1细胞）与脾细胞（效应细胞）的反应检测TQ33。对小鼠NK细胞活性的影响;采用淋巴细胞转化法观察TQ33对细胞免疫的影响;计算小鼠胸腺／体重及脾脏／体重为脏器系数观察TQ33对小鼠脏器的影响。结果 与对照组比较,TQ33显著增加小鼠腹腔巨噬细胞吞噬功能;对小鼠体液免疫功能有一定的增强作用;可增强小鼠NK细胞活性;对ConA诱导下的小鼠淋巴细胞转化有增强作用;对脏器系数没有显著的影响。结论 凝结芽胞杆菌具有明显的免疫调节作用,预示有良好的应用前景。     

Determinants of immunity to murine salmonellosis: studies involving immunization with lipopolysaccharide-lipid A-associated protein complexes in C3H/HeJ mice

Abstract We have earlier demonstrated that the C3H/HeJ Salmonella hypersusceptible mouse can be protected against infection with this organism by prior immunization with lipopolysaccharide (LPS)-lipid A-associated protein (LAP) complexes, but not with LPS alone. In the current studies, protection has been shown to correlate with the induction of LPS-specific antibody in immunized mice. LPS was demonstrated to be a relevant target antigen for Salmonella immunity since C3H/HeJ mice were afforded higher survival rates when they were challenged with Salmonella that shared the same LPS O-antigen as the vaccine. Although low levels of LPS-specific antibody can be detected 14 days after immunization with LAP-LPS, significant antibody is present only after 21–28 days. In addition, anti-LAP specific antibodies can be detected after 14 days of immunization with LAP-LPS. Adoptive transfer of either day 28 anti-LAP-LPS immune serum or day 28 LAP-LPS immune splenocytes alone to naive recipients affords mice minimal, if any, survival against lethal S. typhimurium LT2 challenge. In contrast, transfer of day 28 anti-LAP-LPS immune serum and day 28 LAP-LPS immune splenocytes together is able to transfer Salmonella immunity to naive C3H/HeJ mice. Further, equivalent transfer of only day 28 anti-LAP-LPS immune serum to C3H/HeJ mice immunized 7 days previously with LAP-LPS provides protection similar to that found in mice adoptively transferred with immune cells and serum. These results suggest that a host cellular factor or factors responsive to LAP-LPS, in addition to day 28 anti-LAP-LPS immune serum, may contribute to the protection afforded C3H/HeJ mice following immunization with LAP-LPS.