急性冠状动脉综合征患者外周血中髓系来源抑制性细胞的表达水平研究

目的 探讨单核细胞型髓系来源抑制性细胞(M-MDSC)及相关细胞因子在急性冠状动脉综合征(ACS)患者外周血中的表达水平。方法 采集2020年1月至2021年1月安徽省立医院心血管内科的62例初诊ACS患者、33例稳定性心绞痛(SAP)患者和40例健康对照者(HC)的外周血,采用流式细胞术检测M-MDSC的表达水平;检测粒细胞-巨噬细胞集落刺激因子(GM-CSF)和白细胞介素6(IL-6)水平;检测精氨酸酶-1(Arg-1)mRNA和诱导型一氧化氮合酶(iNOS)mRNA水平。分析M-MDSC在ACS、SAP和HC组中的表达水平,以及与GM-CSF、IL-6、Arg-1和iNOS水平的相关性。比较ACS患者治疗前后,M-MDSC及相关细胞因子的水平变化。结果 与SAP组和HC组比较,ACS组患者外周血中M-MDSC、GM-CSF、IL-6和Arg-1 mRNA水平显著升高(均为P<0.01)。而急性ST段抬高型心肌梗死患者外周血中M-MDSC水平又较急性非ST段抬高型心肌梗死和不稳定性心绞痛患者显著升高(F=28.502,P=0.001)。M-MDSC水平与GM-CSF、IL-6...     

活动性肺结核病患者髓系抑制性细胞的检测分析

目的 研究活动性肺结核病患者、潜伏感染者和健康者髓系抑制性细胞(myeloid-derived suppressor cells,MDSCs)的产生及分布特性.方法 活动性肺结核病患者均为确诊的住院患者,潜伏感染者及健康者经ELISPOT检查确定.外周静脉血用CD14、HLA-DR、CD11b、CD33抗体共染色,采用流式细胞术分析.结果 通过对78例活动性肺结核病患者、30例潜伏感染者及66例健康者的对比分析发现,活动性肺结核病患者CD14-HLA-DR-CD33+ CD11bhighMDSCs细胞比例高于潜伏感染者(P=0.0238),也高于健康者( P＜0.001),而潜伏感染者与健康者CD14-HLA-DR- CD33+ CD11bhighMDSCs细胞比例差异无统计学意义；活动性肺结核病患者CD14+ HLA-DR-MDSCs比例与潜伏感染者及健康者比较差异无统计学意义.活动性肺结核病患者外周血转化生长因子β1水平高于健康对照组(P＜0.05).结论 活动性肺结核病患者CD14- HLA-DR- CD33+CD11bhigh MDSCs比例显著增高,提示活动性肺结核病可能诱导特定的MDSCs亚群,发挥免疫抑制作用,促进结核病的发生及发展.     

细粒棘球绦虫感染小鼠肝脏髓源抑制性细胞 与调节性T细胞比例动态变化

目的　分析细粒棘球蚴感染小鼠肝脏髓源抑制性细胞（MDSCs）和调节性T（Treg）细胞比例动态变化,探讨其可能的生物学意义。方法　将30只6 周龄雌性BALB/c 小鼠随机分为感染组和对照组,每组15只。感染组每只小鼠腹腔注射细粒棘球绦虫原头节约2 000个,对照组注射等体积生理盐水。感染后3、6、12个月（感染早、中、晚期）收集小鼠肝脏白细胞,采用流式细胞术检测其中MDSCs 及其亚型M?MDSCs、PMN?MDSCs 与Treg细胞比例。结果　感染组小鼠感染后3、6、12个月肝脏白细胞中MDSCs 比例分别为（1.61 ± 0.36）%、（5.68 ± 0.69）%和（16.18 ± 0.69）%,对照组分别为（2.19 ± 0.42）%、（0.99 ± 0.07）%和（4.18 ± 0.84）%,感染后6个月和12个月两组差异均有统计学意义（P均 < 0.01）;感染组小鼠感染3、6、12个月后肝脏白细胞中M?MDSCs 比例分别为（0.69 ± 0.27）%、（5.30 ± 0.72）%和（10.75 ± 0.29）%,对照组分别为（0.42 ± 0.24）%、（0.69 ± 0.02）%和（2.12 ± 0.13）%,感染后6个月和12个月两组差异均有统计学意义（P 均< 0.01）;感染组小鼠感染后3、6、12个月肝脏白细胞中PMN?MDSCs 比例分别为（0.93 ± 0.23）%、（0.32 ± 0.02）%和（5.14 ± 1.03）%,对照组分别为（1.77 ± 0.26）%、（0.28 ± 0.05）%和（1.99 ± 0.90）%,感染后3个月和12个月两组差异均有统计学意义（P均 < 0.05）。感染组小鼠感染后3、6、12个月肝脏白细胞中Treg细胞比例分别为（3.35 ± 0.14）%、（6.24 ± 0.38）%和（3.41 ± 0.07）%,对照组分别为（3.48 ± 0.46）%、（3.65 ± 0.45）%和（3.12 ± 0.12）%,感染后6个月和12个月两组差异均有统计学意义（P均＜0.01）。结论　小鼠感染细粒棘球蚴6个月和12个月后,其肝脏白细胞中MDSCs与Treg细胞比例增加,前者比例变化更加明显,以M?MDSCs为主;以上提示M?MDSCs可能在小鼠感染细粒棘球蚴中后期发挥主要免疫抑制作用。     

细粒棘球绦虫感染小鼠肝脏髓源抑制性细胞 与调节性T细胞比例动态变化

目的　分析细粒棘球蚴感染小鼠肝脏髓源抑制性细胞（MDSCs）和调节性T（Treg）细胞比例动态变化，探讨其可能的生物学意义。方法　将30只6 周龄雌性BALB/c 小鼠随机分为感染组和对照组，每组15只。感染组每只小鼠腹腔注射细粒棘球绦虫原头节约2 000个，对照组注射等体积生理盐水。感染后3、6、12个月（感染早、中、晚期）收集小鼠肝脏白细胞，采用流式细胞术检测其中MDSCs 及其亚型M?MDSCs、PMN?MDSCs 与Treg细胞比例。结果　感染组小鼠感染后3、6、12个月肝脏白细胞中MDSCs 比例分别为（1.61 ± 0.36）%、（5.68 ± 0.69）%和（16.18 ± 0.69）%，对照组分别为（2.19 ± 0.42）%、（0.99 ± 0.07）%和（4.18 ± 0.84）%，感染后6个月和12个月两组差异均有统计学意义（P均 < 0.01）；感染组小鼠感染3、6、12个月后肝脏白细胞中M?MDSCs 比例分别为（0.69 ± 0.27）%、（5.30 ± 0.72）%和（10.75 ± 0.29）%，对照组分别为（0.42 ± 0.24）%、（0.69 ± 0.02）%和（2.12 ± 0.13）%，感染后6个月和12个月两组差异均有统计学意义（P 均< 0.01）；感染组小鼠感染后3、6、12个月肝脏白细胞中PMN?MDSCs 比例分别为（0.93 ± 0.23）%、（0.32 ± 0.02）%和（5.14 ± 1.03）%，对照组分别为（1.77 ± 0.26）%、（0.28 ± 0.05）%和（1.99 ± 0.90）%，感染后3个月和12个月两组差异均有统计学意义（P均 < 0.05）。感染组小鼠感染后3、6、12个月肝脏白细胞中Treg细胞比例分别为（3.35 ± 0.14）%、（6.24 ± 0.38）%和（3.41 ± 0.07）%，对照组分别为（3.48 ± 0.46）%、（3.65 ± 0.45）%和（3.12 ± 0.12）%，感染后6个月和12个月两组差异均有统计学意义（P均＜0.01）。结论　小鼠感染细粒棘球蚴6个月和12个月后，其肝脏白细胞中MDSCs与Treg细胞比例增加，前者比例变化更加明显，以M?MDSCs为主；以上提示M?MDSCs可能在小鼠感染细粒棘球蚴中后期发挥主要免疫抑制作用。     

树突状细胞在寄生虫感染中的作用

树突状细胞是一类重要的抗原提呈细胞 ,在宿主针对寄生虫感染的免疫应答过程中起到了重要作用。该文通过分析血吸虫、疟原虫、利什曼原虫、弓形虫、锥虫、丝虫等寄生虫感染的研究现状 ,对树突状细胞在诱导机体保护性免疫以及参与形成寄生虫免疫逃避中的作用机制作进一步介绍     

自身免疫性肝炎患者外周血中髓系来源抑制性细胞频率变化

目的 探讨自身免疫性肝炎(autoimmune hepatitis,AIH)患者外周血中髓系来源抑制性细胞(myeloid-derived suppressor cells,MDSCs)频率及其与疾病的关系.方法　采集22例AIH患者和24例健康对照者外周血,用流式细胞仪分析MDSCs频率,对患者MDSCs频率与肝脏生...     

寄生虫感染和细胞色素P450

疟原虫、血吸虫、丝虫、钩虫、肝片吸虫、利什曼原虫、锥虫和阿米巴等１２种寄生虫感染可损害宿主肝脏的细胞色素Ｐ４５０酶系统功能，影响宿主对药物以及外源性和内源性生物活性物质的代谢能力，本文对其在宿主引起的这类变化的可能机制和某些细胞色素Ｐ４５０化学诱导剂对寄生虫感染宿主的作用加以综述。     

树突状细胞与寄生虫感染

自1973年Steinman和Cohn首次报道树突状细胞（dendritic cell,DC）以来,人们对DC的认识不断深入。DC是目前已知的体内功能最强的一类专职抗原提呈细胞,同时也是初次免疫应答的始动者,能强有力地激活初始T细胞,并决定机体免疫应答的方向,其在寄生虫感染中的作用越来越受到人们的重视。本文就DC的来源、主要功能及其在寄生虫感染免疫中的作用综述如下。     

NK细胞免疫治疗在髓系恶性肿瘤中的研究进展

自然杀伤(natural killer,NK)细胞来源于CD34+造血干细胞,是天然免疫系统的重要组成部分,因其可以在没有抗原预敏的条件下以主要组织相容性复合体(major histocompatibility complex,MHC)非限制性方式快速杀伤耙细胞而成为免疫治疗的研究热点.     

髓系白血病细胞在中枢神经系统发育1例

<正>患者,男,48岁,主因确诊急性粒细胞白血病M1型6个月余,完全缓解4个月余,患者出现间断头痛,伴左眼视物重影,为进一步化疗于2013-06-24入院。患者于6个月前无明显诱因出现全身散在瘀斑,颜色加重,血常规:WBC 292.5×109/L,白细胞无法分类,Hb 76g/L,PLT 11×109/L;血涂片检查:可见大量原始细胞,约占91%;骨髓涂片细胞形态学检查:骨髓增生明显活跃,粒系增生显著,     

髓源性抑制细胞与肺部疾病的潜在联系

髓源性抑制细胞(myeloid-derived suppressor cells,MDSCs)是一种以调节T细胞反应和抑制炎症反应为特征的异质性免疫细胞群.最新研究显示,MDSCs在肺部疾病中有复杂的作用.在这篇综述中,我们讨论了MDSCs作为一种生物标志物和治疗靶点在肺部疾病的潜在作用,特别是肺癌、肺损伤、COPD、哮喘.     

Expression and significance of peripheral myeloid-derived suppressor cells in chronic hepatitis B patients

Background

Myeloid-derived suppressor cells (MDSCs) exert their suppressive effects on multiple immune response and contribute to the development of many diseases. However, limited data is available on the involvement of MDSCs in human chronic HBV infection.

Ageing and myeloid-derived suppressor cells: possible involvement in immunosenescence and age-related disease

Infections, cancer and autoimmune diseases occur more frequently in the elderly, and although many factors contribute to this, the age-related remodelling of the immune system, termed immunosenescence, plays a major role. Over the last two decades, studies have evaluated the effect of ageing on both the adaptive and innate arms of the immune system and demonstrated compromised function in several cells including lymphocytes (naïve, effector and memory), regulatory T and B cells, monocytes, neutrophils and NK cells. In addition, a well-documented feature of ageing is the increase in systemic inflammatory status (inflammageing), with raised serum levels of IL6, TNFα and CRP as well as reduced IL10. Recently, myeloid-derived suppressor cells have been the focus of many reports as these cells show immunosuppressive properties and are present in higher frequency during infections, cancer and autoimmunity. Importantly, there have been publications showing increased numbers of myeloid-derived suppressor cells in aged mice and humans. In this review, we discuss the current literature on myeloid-derived suppressor cells, their possible role in altered immune function in the elderly, and whether it may be possible to manipulate these cells to alleviate age-related immune dysfunction.     

髓源抑制细胞与慢性胃炎至胃癌演变的相关性

目的 探讨健康者、慢性胃炎、胃上皮内瘤变及胃癌患者外周血髓源抑制细胞( MDSC)比例变化与细胞免疫功能之间的关联.方法 收集2011年2月至7月间129份外周血标本,包括32例健康志愿者、48例慢性胃炎患者、27例胃上皮内瘤变患者及22例胃癌患者.采用流式细胞术对外周血的MDSC、T淋巴细胞亚群、调节性T细胞(Treg)的比例进行检测.采用单因素方差分析和Pearson及Spearman相关分析进行统计学处理.结果 胃癌组外周血中MDSC、调节性T细胞(Treg)、CD8+T淋巴细胞的比例最高[(9.63±3.24)％,(10.03±1.26)％,(69.45±3.42)％],健康组中最低[(0.92±0.33)％,(4.12±0.99)％,(32.35±4.83)％],胃上皮内瘤变组[(5.13±1.30)％,(7.54±0.79)％,(53.26±4.30)％)]低于胃癌组但高于慢性胃炎组[(2.76±0.64)％,(6.28±0.61)％,(42.37±4.02)％];各组间差异均有统计学意义(F=24.85、20.88、37.84,P值均＜0.05).相反,CD4+T淋巴细胞的比例在健康组最高,为(65.10±4.10)％,在慢性胃炎组(55.15％±4.00％)、胃上皮内瘤变组(42.23％±3.91％)和胃癌组(26.84％±3.69％)中依次降低,各组间差异有统计学意义(F=46.80,P＜0.05).外周血MDSC比例与胃癌TNM分期呈正相关(r=0.856,P＜0.01).外周血MDSC比例与Treg比例呈正相关(r=0.862,P＜0.01),与CD4+/CD8+T淋巴细胞比值呈负相关(r=-0.768,P＜0.01).结论 外周血MDSC比例的升高与人体细胞免疫功能密切相关,可能在慢性胃炎演变至胃癌的肿瘤逃逸过程中起至关重要的作用.     

Increased frequency and clinical significance of myeloid-derived suppressor cells in human colorectal carcinoma

AIM: To investigate the frequency and clinical significance of the myeloid-derived suppressor cells (MDSC) in human colorectal carcinoma (CRC).METHODS: Samples of peripheral blood and tumor tissue from 49 CRC patients were analyzed. Mononuclear cells were isolated by Ficoll-Hypaque density gradient centrifugation and were subjected to a flow cytometry-based immunophenotypic analysis.RESULTS: A considerable increase in the percentage of CD33⁺HLA-DR^- MDSCs was observed in the peripheral blood (1.89% ± 0.75%) and tumor tissues (2.99% ± 1.29%) of CRC patients as compared with that in the peripheral blood of healthy controls (0.54% ± 0.35%). This expanded CD33⁺HLA-DR^- subset exhibited immature myeloid cell markers, but not lineage markers, and showed up-regulation of CD18/CD11b expression as compared with the MDSCs from healthy donors. Further studies showed that the MDSC proportion in CRC peripheral blood was correlated with nodal metastasis(P = 0.023), whereas that in tumor tissues was correlated with nodal/distant metastasis (P = 0.016/P = 0.047) and tumor stage (P = 0.028), suggesting the involvement of MDSCs in CRC tumor development.CONCLUSION: Characterization of MDSCs in CRC suggests the clinical significance of circulating and tumor-infiltrating MDSCs and may provide new insights into the CRC immunotherapy targeting MDSCs.     

Correlation between circulating myeloid-derived suppressor cells and Th17 cells in esophageal cancer

AIM: To perform a comprehensive investigation into the potential correlation between circulating myeloidderived suppressor cells (MDSCs) and Th17 cells in esophageal cancer (ECA). METHODS: A total of 31 patients newly diagnosed with ECA and 26 healthy subjects were included in the current study. The frequencies of MDSCs and Th17 cells in peripheral blood were determined by flow cytometry. The mRNA expression of cytokines, arginase 1 (Arg1) and inducible NO synthase (iNOS) in peripheral blood mononuclear cells (PBMCs) and plasma Arg1 were assessed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: There was an increased prevalence of MDSCs in the peripheral blood from ECA patients (15.21% ± 2.25%) when compared with healthy control (HC) (1.10% ± 0.12%, P 0.0001). The plasma levels of Arg1 in ECA patients were significantly higher than those in HC (28.28 ± 4.10 ng/mL vs 9.57 ± 1.51 ng/ mL, P=0.0003). iNOS mRNA levels in the peripheral blood of ECA patients also showed a threefold increase compared with HC (P=0.0162). The frequencies of Th17 cells (CD4 + IL-17A + ) were significantly elevated in ECA patients versus HC (3.50% ± 0.33% vs 1.82% ± 0.19%, P=0.0001). Increased mRNA expression of IL-17 and ROR-γt was also observed in ECA patients compared with HC (P=0.0041 and P=0.0004, respectively), while the mRNA expression of IL-6 and tumor necrosis factor-α (TNF-α) showed significant decreases (P=0.0049 and P 0.0001, respectively). No obvious correlations were found between the frequencies of MDSCs and Th17 cells in the peripheral blood from ECA patients(r=-0.1725, P=0.3534). Arg1 mRNA levels were positively correlated with levels of IL-6 (r=0.6404, P=0.0031) and TNF-α (r=0.7646, P=0.0001). Similarly, iNOS mRNA levels were also positively correlated with levels of IL-6 (r=0.6782, P=0.0007) and TNF-α (r=0.7633, P 0.0001). CONCLUSION: This study reveals the relationship between circulating MDSCs and Th17 cells, which may lead to new immunotherapy approaches for ECA based on the associated metabolites and cytokines.     

Circulating myeloid-derived suppressor cells in patients with pancreatic cancer

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are heterogeneous cell types that suppress T-cell responses in cancer patients and animal models, some MDSC subpopula-tions are increased in patients with pancreatic cancer. The present study was to investigate a specific subset of MDSCs in patients with pancreatic cancer and the mechanism of MDSCs increase in these patients.
METHODS: Myeloid cells from whole blood were collected from 37 patients with pancreatic cancer, 17 with cholangiocarcinoma, and 47 healthy controls. Four pancreatic cancer cell lines were co-culturedwithnormalperipheralbloodmononuclearcells(PBMCs) to test the effect of tumor cells on the conversion of PBMCs to MDSCs. Levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and arginase activity in the plasma of cancer patients were analyzed by enzyme-linked immunosorbent assay.
RESULTS: CD14+/CD11b+/HLA-DR- MDSCs were increased in patients with pancreatic or bile duct cancer compared with those in healthy controls, and this increase was correlated with clinical cancer stage. Pancreatic cancer cell lines induced PBMCs to MDSCs in a dose-dependent manner. GM-CSF and arginase activity levels were significantly increased in the se-rum of patients with pancreatic cancer.
CONCLUSIONS: MDSCsweretumorrelated:tumorcellsinduced PBMCs to MDSCs in a dose-dependent manner and circulating CD14+/CD11b+/HLA-DR- MDSCs in pancreatic cancer patients were positively correlated with tumor burden. MDSCs might be useful markers for pancreatic cancer detection and progression.     

自身免疫性肝炎患者肝组织IL-35表达和外周血髓样抑制细胞百分比变化临床意义探讨

目的 观察自身免疫性肝炎(AIH)患者肝组织白介素-35(IL-35)表达和外周血髓样抑制细胞(MDSCs)百分比变化的临床意义.方法 2017年5月～2020年2月我院收治的35例AIH患者,给予泼尼松或波尼松联合硫唑嘌呤治疗.行肝穿活组织检查,根据界面破坏范围和细胞浸润深度将患者分为轻度、中度和重度组.采用West...     

Respiratory and systemic monocytes,dendritic cells,and myeloid-derived suppressor cells in COVID-19: Implications for disease severity

Since the beginning of the SARS-CoV-2 pandemic in 2020, researchers worldwide have made efforts to understand the mechanisms behind the varying range of COVID-19 disease severity. Since the respiratory tract is the site of infection, and immune cells differ depending on their anatomical location, studying blood is not sufficient to understand the full immunopathogenesis in patients with COVID-19. It is becoming increasingly clear that monocytes, dendritic cells (DCs), and monocytic myeloid-derived suppressor cells (M-MDSCs) are involved in the immunopathology of COVID-19 and may play important roles in determining disease severity. Patients with mild COVID-19 display an early antiviral (interferon) response in the nasopharynx, expansion of activated intermediate monocytes, and low levels of M-MDSCs in blood. In contrast, patients with severe COVID-19 seem to lack an early efficient induction of interferons, and skew towards a more suppressive response in blood. This is characterized by downregulation of activation markers and decreased functional capacity of blood monocytes and DCs, reduced circulating DCs, and increased levels of HLA-DR^loCD14⁺ M-MDSCs. These suppressive characteristics could potentially contribute to delayed T-cell responses in severe COVID-19 cases. In contrast, airways of patients with severe COVID-19 display hyperinflammation with elevated levels of inflammatory monocytes and monocyte-derived macrophages, and reduced levels of tissue-resident alveolar macrophages. These monocyte-derived cells contribute to excess inflammation by producing cytokines and chemokines. Here, we review the current knowledge on the role of monocytes, DCs, and M-MDSCs in COVID-19 and how alterations and the anatomical distribution of these cell populations may relate to disease severity.