牙髓炎症中白细胞介素-17调节单核细胞功能和分化的研究

目的 探讨牙髓炎症中白细胞介素(IL)-17募集单核细胞并调节其分化的作用。方法 肿瘤坏死因子(TNF-α)刺激牙髓细胞,模拟炎症状态,实时荧光定量PCR技术(RT-qPCR)、酶联免疫吸附法(ELISA)检测IL-17的表达;IL-17重组蛋白刺激牙髓细胞,收集培养基上清,通过Transwell小室实验检测IL-17或受IL-17刺激的牙髓细胞培养基上清对单核细胞的趋化作用;采用结晶紫染色和吞噬实验分别检测IL-17或受IL-17刺激的牙髓细胞培养基上清对单核细胞贴壁和吞噬的影响;IL-17刺激人单核细胞系(THP-1)细胞,RT-qPCR和ELISA分别检测TNF-α、IL-1β的表达,流式细胞检测THP-1细胞表面标志物分子簇80(CD80)的表达变化。结果 牙髓炎症中IL-17表达上调,IL-17使单核细胞贴壁增多,吞噬功能增强,TNF-α、IL-1β及CD80表达上调。结论 IL-17在牙髓炎症中高表达,其本身对单核细胞有趋化作用,并可通过刺激牙髓细胞产生趋化因子2(CCL2)放大趋化作用;IL-17可以调控单核细胞向巨噬细胞分化。     

Medline(PubMed)免疫学杂志文献搜索引擎开发研究

为了方便免疫学和相关学科工作者方便快捷、准确地查阅免疫学杂志文献,开发和利用NCBI的Medline数据库的免疫学杂志文献资源。从Medline(PubMed)中检索并列出160种有关免疫学的杂志名录,制作了每种杂志及部分杂志年份相应的超级链接,组成一个有关免疫学杂志文献的搜索引擎。此搜索引擎能快捷、准确、动态地检索160种免疫学杂志全部文献题录及部分杂志各年的文献题录,并可在PubMed中进一步检索出文献的摘要和部分全文。     

Calcineurin inhibitors suppress acute graft-versus-host disease via NFAT-independent inhibition of T cell receptor signaling

Inhibitors of calcineurin phosphatase activity (CNIs) such as cyclosporin A (CsA) are widely used to treat tissue transplant rejection and acute graft-versus-host disease (aGVHD), for which inhibition of gene expression dependent on nuclear factor of activated T cells (NFAT) is the mechanistic paradigm. We recently reported that CNIs inhibit TCR-proximal signaling by preventing calcineurin-mediated dephosphorylation of Lck^S59, an inhibitory modification, raising the possibility of another mechanism by which CNIs suppress immune responses. Here we used T cells from mice that express Lck^S59A, which cannot accept a phosphate at residue 59, to initiate aGVHD. Although CsA inhibited NFAT-dependent gene upregulation in allo-aggressive T cells expressing either Lck^WT or Lck^S59A, it was ineffective in treating disease when the T cells expressed Lck^S59A. Two important NFAT-independent T cell functions were found to be CsA-resistant in Lck^S59A T cells: upregulation of the cytolytic protein perforin in tissue-infiltrating CD8⁺ T cells and antigen-specific T/DC adhesion and clustering in lymph nodes. These results demonstrate that effective treatment of aGVHD by CsA requires NFAT-independent inhibition of TCR signaling. Given that NFATs are widely expressed and off-target effects are a major limitation in CNI use, it is possible that targeting TCR-associated calcineurin directly may provide effective therapies with less toxicity.     

One dose of SARS-CoV-2 vaccine exponentially increases antibodies in individuals who have recovered from symptomatic COVID-19

BACKGROUNDThe COVID-19 vaccines currently in use require 2 doses to achieve optimal protection. Currently, there is no indication as to whether individuals who have been exposed to SARS-CoV-2 should be vaccinated, or whether they should receive 1 or 2 vaccine doses.METHODSWe tested the antibody response developed after administration of the Pfizer/BioNTech vaccine in 124 health care professionals, of whom 57 had a previous history of SARS-CoV-2 exposure with or without symptoms.RESULTSPostvaccine antibodies in SARS-CoV-2–exposed individuals increased exponentially within 5 to 18 days after the first dose compared to naive subjects (P < 0.0001). In a multivariate linear regression (LR) model we showed that the antibody response depended on the IgG prevaccine titer and on the exposure to SARS-CoV-2. In symptomatic SARS-CoV-2–exposed individuals, IgG reached a plateau after the second dose, and those who voluntarily refrained from receiving the second dose (n = 7) retained their antibody response. Gastrointestinal symptoms, muscle pain, and fever markedly positively correlated with increased IgG responses. By contrast, all asymptomatic/paucisymptomatic and unexposed individuals showed an important increase after the second dose.CONCLUSIONOne vaccine dose is sufficient in symptomatic SARS-CoV-2–exposed subjects to reach a high titer of antibodies, suggesting no need for a second dose, particularly in light of current vaccine shortage.TRIAL REGISTRATIONClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT04387929","term_id":"NCT04387929"}}NCT04387929.FUNDINGDolce & Gabbana and the Italian Ministry of Health (Ricerca corrente).     

MAGE-A1在食管癌中的表达及其与肿瘤细胞增殖的关系

目的:研究食管癌中肿瘤特异性抗原MAGE-A1,Ki-67的表达及其相关性,探讨他们与食管癌生物学行为及生存时间的关系.方法:免疫组化SP法,利用鼠抗人MAGE-A1,Ki-67单克隆抗体检测60例食管癌标本中MAGE-A1,Ki-67表达水平.结果:60例食管癌中MAGE-A1表达率为83.3%(50/60),高表达率为10%(6160),低表达率为73.3%(44/60),正常组织表达率为0%,食管癌和正常组织之间的表达具有显著性差异(P＜0.001).Ki-67表达率为93.3%(56/60),高表达率为70%(42/60),低表达率为23.3%(14/60),正常组织表达率为13.3%(4/30),食管癌和正常组织之间的表达具有显著性差异(P＜0.001).MAGE-A1与分化程度有关(P＜0.05),Ki-67与年龄、分化程度、病理类型有关(P＜0.05).MAGE-A1阳性表达的高低与Ki-67阳性表达的高低呈负相关(r=-2.91,P＜0.05).MAGE-A1阳性患者的生存时间明显高于阴性者.结论:MAGE-A1在食管癌中有较高的表达,并且与细胞增殖相关,正常组织不表达,MAGE-A1阳性患者的预后好,有望作为免疫治疗的靶点.     

307例急性髓系白血病在WHO分型标准中的探讨

目的：通过对本组病例研究，提高对WHO分型诊断标准的认识。方法：选择2004-2005年在我院确诊的307例急性髓系白血病（AML），以形态学、免疫表型、融合基因等检测进行分析探讨。结果：按WHO分型诊断标准有14例原始细胞在20％～30％之间的患者被确诊为AML。免疫表型在髓系白血病中MPO、CD13、CD33表达最强，分别为96．77％、94．67％、91．53％。对M0的诊断有特异性，CD34、CD33达99％以上。融合基因检测：AML-M2b中90％以上AML1／ETO融合基因阳性，提示t（8；21）（q22；q22）易位。AML-M3中89．28％PML／RARα融合基因阳性，提示t（15；17）（q22；q12）易位。AML-M4EO中85％的CBFβ／MYH11融合基因阳性，提示inv（16）（p13；q22）。结论：WHO分型标准综合了传统的形态学分型，加入免疫学，融合基因等检测技术，结合临床特点等信息对AML进行分型，提高了对AML的诊断符合率。与FAB相比，更具有完全性、合理性、科学性，是AML分型的发展方向。     

SIRPγ-expressing cancer stem-like cells promote immune escape of lung cancer via Hippo signaling

Cancer stem-like cells (CSLCs) acquire enhanced immune checkpoint responses to evade immune cell killing and promote tumor progression. Here we showed that signal regulatory protein γ (SIRPγ) determined CSLC properties and immune evasiveness in a small population of lung adenocarcinoma (LUAD) cancer cells. A SIRPγ^hi population displayed CSLC properties and transmitted the immune escape signal through sustaining CD47 expression in both SIRPγ^hi and SIRPγ^lo/– tumor cells. SIRPγ bridged MST1 and PP2A to facilitate MST1 dephosphorylation, resulting in Hippo/YAP activation and leading to cytokine release by CSLCs, which stimulated CD47 expression in LUAD cells and consequently inhibited tumor cell phagocytosis. SIRPγ promoted tumor growth and metastasis in vivo through YAP signaling. Notably, SIRPγ targeting with genetic SIRPγ knockdown or a SIRPγ-neutralizing antibody inhibited CSLC phenotypes and elicited phagocytosis that suppressed tumor growth in vivo. SIRPG was upregulated in human LUAD and its overexpression predicted poor survival outcome. Thus, SIRPγ^hi cells serve as CSLCs and tumor immune checkpoint–initiating cells, propagating the immune escape signal to the entire cancer cell population. Our study identifies Hippo/YAP signaling as the first mechanism by which SIRPγ is engaged and reveals that targeting SIRPγ represents an immune- and CSLC-targeting strategy for lung cancer therapy.