肿瘤患者CD8+T细胞中CD28表达的研究进展

CD28与B7结合形成的共刺激信号是T细胞激活的第二信号,肿瘤患者CD8^＋T细胞上CD28分子在肿瘤免疫中发挥着重要作用。人体抗肿瘤免疫主要由CD8^＋T细胞介导,根据CD28的表达与否可将CD8^＋T细胞分为细胞毒T细胞（CD8^＋CD28^＋,CTL）和抑制性T细胞（CD8^＋C28^-,Ts）。CTL是体内杀伤肿瘤细胞的主要功能性细胞之一,当该细胞与肿瘤接触时,通过共刺激信号而被激活,发挥其对肿瘤细胞的杀伤作用;Ts在机体的免疫耐受中发挥作用。现就肿瘤患者CD8^＋T细胞上CD28的表达作一综述。     

非霍奇金淋巴瘤患者外周血中CD4＋CD25＋调节性T细胞亚群变化初探

目的：检测非霍奇金淋巴瘤（non—Hodgkin’s lymphoma,NHL）患者外周血中CD4＋CD25＋调节性T细胞（CD4＋CD25＋regulatoryTcell,Treg）的改变,探讨Treg与NHL的相关性。方法：病例组（n=60）为本院收治的初诊NHL患者,对照组（n=60）为本院健康体检者,用流式细胞技术联合标记CD4、CD25检测对照组及病例组化疗前、化疗后的外周血中CD4＋CD25＋调节性T细胞的分布特点。结果：（1）病例组化疗前外周血中CD4＋细胞比例显著低于对照组（P〈0．05）,CD4＋CD25＋调节性T细胞比例显著高于对照组（P〈0．05）;（2）病例组化疗后,CD4＋细胞比例明显高于化疗前（P〈0．05）,CD4＋CD25＋调节性T细胞比例明显低于化疗前（P〈0．05）;（3）病例组化疗后CD4＋细胞比例与对照组无显著差异（P〉0．05）,而CD4＋CD25＋调节性T细胞比例显著高于对照组（P〈0．05）。结论：非霍奇金淋巴瘤患者外周血中CD4＋CD25＋调节性T细胞比例升高,存在机体免疫抑制,化疗可降低CD4＋CD25＋调节性T细胞比例。     

生殖器疱疹初发患者外周血淋巴细胞检测结果分析

目的检测生殖器疱疹初发患者（GH）外周血T淋巴细胞亚群、NK细胞和B细胞的表达水平,探讨其发病机制与细胞免疫功能之间的关系。方法应用流式细胞仪检测20例初发生殖器疱疹患者外周血T淋巴细胞亚群、NK细胞和B细胞的表达水平,并与60例复发性生殖器疱疹患者（RGH）、35例健康对照者外周血检测结果相比较。结果（1）初发组和对照组相比,除NK细胞降低差异有显著性外,其他差异无显著性;（2）初发组与复发组相比,初发组T细胞、CD4^＋细胞、CD4^＋／CD8^＋均高于复发组,CD8^＋细胞百分比低于后者,差异有显著性;B细胞、NK细胞比例差异无显著性;（3）复发组与对照组相比,外周血中T细胞、CD4^＋细胞、NK细胞所占比例,CD4^＋／CD8^＋均降低,差异有显著性;CD8^＋细胞百分比升高,差异有显著性;B细胞比例差异无显著性。结论生殖器疱疹初发患者存在细胞免疫功能异常。     

SLE带状疱疹患者外周血CD4~+CD28~+和CD4~+CD25~+FoxP3~+调节性T细胞的表达及相关性研究

目的:检测系统性红斑狼疮(systemic lupus erythematosus,SLE)合并带状疱疹患者外周血CD4~+CD28~+和CD4~+CD25~+Fox P3~+调节性T细胞的表达及相关性,探讨其在SLE合并带状疱疹发病中的临床意义。方法:采用流式细胞术检测30例SLE患者、30例SLE合并带状疱疹患者及30例健康对照者外周血中CD4~+/CD8~+T淋巴细胞亚群表面CD28的表达及CD4~+CD25~+Fox P3~+Treg细胞的表达水平,并分析SLE合并带状疱疹患者外周血CD4~+CD28~+和CD4~+CD25~+Fox P3~+调节性T细胞表达的相关性。结果:SLE合并带状疱疹组患者急性期外周血CD4~+T淋巴细胞比率、绝对计数显著降低,CD4~+、CD8~+T淋巴细胞表面的CD28表达下调,CD4~+CD25~+Fox P3~+Treg细胞水平显著高于SLE组及健康对照组,SLE合并带状疱疹组患者外周血CD4~+CD25~+Fox P3~+Treg水平与CD4~+CD28~+水平成负相关(P均0.05)。结论:SLE合并带状疱疹患者CD4~+、CD8~+T细胞活化异常,CD4~+CD25~+Fox P3~+Treg细胞可能参与抑制了T细胞的活化。     

宫颈癌患者外周血CD4+CD25+high调节性T细胞的表达及意义

目的:探讨宫颈癌患者外周血中CD4~ CD25~( high)调节性T(regulator T cells,Tr)的表达及意义。方法:采用流式细胞术检测52例宫颈癌患者,35例健康女性外周血中CD4~ CD25~( high)Tr、细胞毒性T细胞(cytotoxic T lymphocytes,CTL)和NK细胞,采用ELISA检测血清中-干扰素(interferon,IFN-)的表达水平。结果:宫颈癌患者外周血CD4~ CD25~( high)Tr占CD4~ T淋巴细胞的百分比为(7.18±2.32)%,高于健康女性组(P<0.05);宫颈癌患者外周血CD4~ CD25~( high)Tr水平与CTL、NK细胞及IFN-水平呈负相关。结论:宫颈癌患者外周血中具免疫抑制活性的CD4~ CD25~( high)Tr水平较高,参与宫颈癌患者的肿瘤免疫抑制。     

不同临床类型乙型病毒感染者外周血T细胞亚群与血清HBVDNA载量及HBeAg滴度相关性分析

目的：探讨慢性乙型肝炎病毒（HBV）感染患者外周血T细胞亚群与血清HBVDNA载量及HbeAg滴度的关系。方法：选取103名HBV感染患者和20名健康者为研究对象。流式细胞术检测外周血T细胞亚群,聚合酶链式反应及酶免疫分析法分别检测血清HBVDNA载量及HbeAg滴度。结果：慢性乙型肝炎患者和慢性HBV携带者外周血CD3可、CD4T淋巴细胞亚群百分数低于健康对照组,结果有统计学意义（P〈0．05或0．01;而CD8＋T细胞亚群则呈现相反趋势,结果亦有统计学意义（P〈0．05或0．01）。HBeAg阴性组中,HBVDNA水平与CD8T细胞亚群百分数呈正相关（r=0．567,P〈0．01）,与CD47CD8＋T细胞亚群百分数比值呈负相关（r=-0．601,P〈0．01）,而与CD3＋T、CD4＋T细胞亚群百分数无相关性。HBeAg阳性组中,HBVDNA水平及HbeAg滴度与cD3＋1r、cD41、CD8叮细胞百分数及CD47CD8＋T细胞百分数均无相关性（P〉0．05）。结论：不同临床类型的慢性乙型肝炎病毒感染患者外周血T细胞亚群存在不同程度细胞免疫功能降低和细胞免疫调节异常。HbeAg阴性的HBV感染患者,其血清HBVDNA水平与外周血T淋巴细胞免疫存在相关性。     

肾移植后恶性肿瘤患者调节性免疫细胞的变化研究

目的:探讨肾移植后发生恶性肿瘤患者调节性免疫细胞的变化。方法:收集2010年5月-2018年3月来我院进行肾移植手术的患者,肿瘤组共20例患者,病理诊断为肾脏及输尿管恶性肿瘤,对照组共20例患者,移植肾功能稳定;分离各组患者外周血淋巴细胞,流式细胞术检测调节性T细胞(Treg细胞)、调节性B细胞(Breg细胞)和滤泡调节性T细胞(Tfr细胞)的比例。结果:流式细胞学检测的结果发现,淋巴细胞中CD4~+T细胞比例在对照组和肿瘤组之间没有显著的差别(P0.05),肿瘤组中CD4+CD25+Foxp3+Treg细胞比例显著的高于对照组,增加了1.29倍(P0.05);CD19+B细胞比例在对照组和肿瘤组之间没有显著的差别(P0.05),肿瘤组中CD19+TGF-β+Breg细胞比例显著的高于对照组,增加了2.69倍(P0.05);肿瘤组中CD4+CXCR5+Foxp3+Tfr细胞比例显著的高于对照组,增加了2.74倍(P0.05)。结论:肾移植后发生恶性肿瘤患者外周血中Treg细胞、Tfr细胞和Breg细胞比例均显著升高,我们的研究为肾移植后临床用药和免疫状态的检测提供了一定的理论依据。     

外周血Treg细胞、T淋巴细胞及其亚群与早期宫颈癌的关系及对淋巴结转移的预测价值研究

摘要 目的：分析外周血Treg细胞、T淋巴细胞及其亚群与早期宫颈癌的关系及对淋巴结转移的预测价值。方法：选择我院自2017年1月至2020年12月接诊的60例接受子宫颈癌根治术及盆腔淋巴清扫术的早期宫颈癌患者作为观察组,另选同期的60例健康体检者作为对照组。比较两组外周血Treg细胞、T淋巴细胞及其亚群水平,使用受试者工作特征曲线（ROC）下面积（AUC）评价外周血Treg细胞、T淋巴细胞及其亚群对淋巴结转移的预测效能。结果：观察组外周血Treg细胞、CD8⁺T细胞水平高于对照组,CD3⁺T细胞、CD4⁺T细胞、CD4⁺/CD8⁺比值均低于对照组（P＜0.05）;观察组术后外周血Treg细胞、CD8⁺T细胞水平较术前降低,CD3⁺T细胞、CD4⁺T细胞、CD4⁺/CD8⁺比值均较术前升高（P＜0.05）;在60例早期宫颈癌患者中,发生淋巴结转移12例;淋巴结转移组术前外周血Treg细胞水平、CD8⁺T细胞高于非淋巴结转移组,CD3⁺T细胞、CD4⁺T细胞、CD4⁺/CD8⁺比值均低于非淋巴结转移组（P＜0.05）;经多因素Logistic回归分析,外周血Treg细胞、CD3⁺T细胞、CD4⁺/CD8⁺比值均是早期宫颈癌患者发生淋巴结转移的独立预测因素（P＜0.05）;经ROC曲线分析,外周血Treg细胞、CD3⁺T细胞联合CD4⁺/CD8⁺比值预测早期宫颈癌患者发生淋巴结转移的AUC为0.910。结论：外周血Treg细胞、T淋巴细胞及其亚群水平与早期宫颈癌的病情演变有关,其中外周血Treg细胞、CD3⁺T细胞联合CD4⁺/CD8⁺比值预测淋巴结转移的效能较好,值得进一步研究应用。     

非小细胞肺癌患者化疗前后外周血T淋巴细胞亚群的变化

目的:探讨非小细胞肺癌(NSCLC)患者细胞化疗前后T淋巴细胞亚群的变化及其意义.方法:采用流式细胞术检测NSCLC患者及健康对照者外周血中CD3+、CD4+、CD8+、CD4+/CD8+及NK细胞的比例.结果:与对照组比较,NSCLC患者化疗前及化疗后CD3+、CD4+、CD4+/CD8+、NK细胞含量均显著降低(P＜0.01);化疗后CD3+、CD4+、CD4+/CD8+、NK细胞比例与化疗前比较均显著升高(P＜0.05);化疗前后CD8+细胞比例无显著变化(P＞0.05).治疗后疾病控制组(DCR)患者的CD3+、CD4+、CD4+/CD8+及NK细胞均显著高于治疗后进展(PD)组患者组(P＜0.05);CD8+细胞的比例无显著性变化(P＞0.05).结论:NSCLC患者细胞免疫功能低下,通过流式细胞术检测患者外周血T淋巴细胞亚群及NK细胞的变化对评估患者的细胞免疫功能及肿瘤化疗疗效具有重要的临床意义.     

急性病毒性肝炎患者外周血T 细胞亚群的检测和分析

目的:检测急性甲、乙型病毒性肝炎患者外周血T淋巴细胞亚群变化,探讨其对疗效和预后意义。方法:采用APAAP桥联酶标法检测115例急性甲、乙型病毒型肝炎患者外周血CD3+、CD4+、CD8+T细胞亚群比例,计算CD4+/CD8+值。并检测了34例患者治疗前后T淋巴细胞亚群变化。结果:115例急性甲、乙型病毒性肝炎患者外周血CD3+、CD4+T细胞比例及CD4+/CD8+值均低于正常对照组(P<0.05),而CD8+T细胞比例均高于正常对照组(P<0.01)。6例无明显疗效者,各亚群比例在治疗前后无显著差异(P>0.05)。28例有明显疗效者,治疗后各亚群比例恢复正常水平,与治疗前相比差别具有统计学意义(P<0.05)。结论:急性甲、乙型病毒性肝炎患者外周血CD4+/CD8+T细胞比值可在一定程度上反映疗效及预后。     

以T细胞受体为基础的免疫疗法研究进展

T细胞是机体抗肿瘤免疫的核心,以T细胞功能调控为基础的免疫检查点疗法已经在多种肿瘤的临床治疗中取得了重大突破,以基因工程化T细胞为基础的过继性免疫细胞疗法在血液瘤治疗中取得了重要进展,免疫治疗已经对肿瘤的临床治疗产生了深刻变革,成为肿瘤临床治疗策略的重要组成部分。T细胞受体（T cell receptor,TCR）赋予了T细胞识别肿瘤抗原的特异性,能够识别由主要组织相容性复合体（major histocompatibility complex,MHC）呈递的包括胞内抗原在内的广泛肿瘤抗原,具有高度的抗原敏感性,因而具有广泛的抗肿瘤应用前景。2022年第一款TCR药物的上市开启了TCR药物开发的新纪元,多项TCR药物临床研究表现出潜在的肿瘤治疗价值。本文综述了以TCR为基础的免疫治疗策略研究进展,包括T细胞受体工程化T细胞（T cell receptor-engineered T cell,TCR-T）和TCR蛋白药物,以及基于TCR信号的其他免疫细胞疗法,以期为以TCR为基础的免疫治疗策略开发提供参考。     

Mathematically modeling dynamics of T cell responses: predictions concerning the generation of memory cells

Mathematical models of T cell population dynamics after infection typically assume that T cells differentiate according to a linear process in which they first become effector cells, and then after some time, differentiate further into memory cells. In this paper, we offer a different mathematical model which can equally well capture T cell dynamics, using data from lymphocytic choriomeningitis (LCMV) infection. Our model assumes that memory cells are intermediates that further differentiate into effector cells only from additional or stronger antigenic stimulation. Our assumption naturally leads to a testable prediction about the generation of T cell memory-that the memory phenotype of T cells should be present in detectable numbers during the expansion phase of the response. We use our model to estimate a rate of differentiation from memory type cells to effectors. We argue that this differentiation assumption, where memory cells are intermediates, captures recent experimental work on T cell differentiation, and hence this new mathematical model could be helpful in doing further studies of T cell population dynamics. We also propose a method of distinguishing the models by examining the ratio of memory T cells detectable long after an infection to the peak numbers of T cells at the end of the expansion phase.     

不同培养基对流式细胞仪分选外周血T细胞的影响

摘要 目的：通过探讨用于流式分选的T细胞体外扩增的无血清培养基，提高过继细胞的增殖能力和活性。方法：采用人外周血淋巴细胞分离管制备外周血单个核细胞，再用流式细胞分选仪从6例健康志愿者的外周血单个核细胞中分选CD3+T细胞到4种常用的培养基中：X-VIVO 15、KBM 581、TexMACS GMP和10 % FBS/1640，观察并记录培养细胞的状态和体外增殖能力。于第3天，第6天和第8天，通过胎盼蓝染色后进行活细胞计数。于第8天用凋亡试剂盒检测扩增细胞的凋亡情况，并用流式细胞分析仪检测细胞的免疫表型。结果：X-VIVO 15、TexMACS GMP和10 % FBS/1640作为流式细胞分选的接收液仅少量细胞碎片，而分选在KBM 581的细胞大量死亡，显著高于X-VIVO 15组（P<0.05）。X-VIVO 15中扩增的细胞数量最多，增殖检测结果显示活细胞在X-VIVO 15中快速增殖且细胞凋亡率显著低于KBM 581 和 TexMACS GMP（P<0.05）。4种培养基扩增的细胞主要呈现效应记忆型。其中，X-VIVO 15中效应记忆型T细胞比例显著高于TexMACS GMP（P<0.05）。TexMACS中效应细胞比例显著高于10 % FBS/1640（P<0.05）。结论：X-VIVO 15无血清培养基扩增流式分选的T细胞具有高增殖能力、细胞活性和记忆表型，适用于经流式分选后细胞的体外扩增。     

Plasticity within the αβ+CD4+ T-cell lineage: when,how and what for?

Following thymic output, αβ⁺CD4⁺ T cells become activated in the periphery when they encounter peptide–major histocompatibility complex. A combination of cytokine and co-stimulatory signals instructs the differentiation of T cells into various lineages and subsequent expansion and contraction during an appropriate and protective immune response. Our understanding of the events leading to T-cell lineage commitment has been dominated by a single fate model describing the commitment of T cells to one of several helper (T_H), follicular helper (T_FH) or regulatory (T_REG) phenotypes. Although a single lineage-committed and dedicated T cell may best execute a single function, the view of a single fate for T cells has recently been challenged. A relatively new paradigm in αβ⁺CD4⁺ T-cell biology indicates that T cells are much more flexible than previously appreciated, with the ability to change between helper phenotypes, between helper and follicular helper, or, most extremely, between helper and regulatory functions. In this review, we comprehensively summarize the recent literature identifying when T_H or T_REG cell plasticity occurs, provide potential mechanisms of plasticity and ask if T-cell plasticity is beneficial or detrimental to immunity.     

ThPOK在T细胞分化发育中的作用

ThPOK（T-helper-inducing POZ/Krueppel-like factor）又被称为Zbtb7b、Zfp67、cKrox,隶属于一个很大的转录因子家族——POK家族。ThPOK最初是被认为与Ⅰ型胶原蛋白基因的转录抑制有关,但近年来的研究发现,ThPOK在T细胞分化过程中至关重要,特别是对CD4^＋T细胞的分化发育起着命运决定的核心作用。该文综述了ThPOK在CD4^＋T细胞分化过程中的作用特点及其与另外两种重要转录因子GATA3和Runx3的相互作用关系,并在此基础上阐述了ThPOK在其他T细胞,如iNKT细胞、γδT细胞及效应CD8^＋T细胞中的作用功能。     

The balancing act of AKT in T cells

The serine/threonine-specific protein kinase AKT is gaining recognition as a major crossroad in numerous cellular signaling pathways through its ability to regulate cell differentiation, proliferation, survival and metabolism. This review focuses on the recent advances in AKT signaling and downstream events in T cells, emphasizing its contrasting role in conventional and regulatory (Treg) Tcell populations. Activation of AKT has been known for many years to be critical in the development and function of conventional Tcells. However, it has just recently been uncovered that AKTexerts an inhibitory effect on Treg generation and suppressor function. These studies have placed AKTat the nexus of Treg development and function, thus opening novel avenues for therapeutic manipulation.     

Dynamics of T cell activation threshold tuning

T lymphocytes are believed to alter their sensitivity to TCR stimulation by means of a tunable cellular activation threshold. We present two modelling examples which show that the concept of a tunable threshold can be made mechanistically plausible. The tunable threshold is treated as an emergent property of the dynamics of the T cell's signalling machinery. In addition, we discuss how the dynamic properties of activation threshold tuning can be determined experimentally with the aid of these two models. We propose a novel 'avidity selection' mechanism for the initial stages of the immune response, based on the properties of the T cell activation threshold tuning mechanism we propose for the commitment to differentiation. Our main finding is that activation threshold tuning allows T cells to respond to relevant ligands with a detection threshold that is (i) uniform across both the T cell repertoire and the secondary lymphoid tissues, while (ii) retaining tolerance to autostimulation. Our analysis indicates that central tolerance enhances the efficiency of peripheral tolerance, casting new light on the role of negative selection in the thymus.     

Generation of HSP60-specific regulatory T cell and effect on atherosclerosis

Although CD4(+)CD25(+) regulatory T cells are pivotal in the suppression of autoimmunity, little is known about the effect of antigen-specific regulatory T cells on the formation of atheromatous plaques. Here, we describe the induction of heat-shock protein 60 (HSP60)-specific CD4(+)CD25(high) T cells by rapamycin (RPM)-treated immature dendritic cells in vitro and explore their effect on plaques in apolipoprotein E-deficient mice. Rapamycin-treated bone marrow-derived dendritic cells (DC) were immature, expressing a low level of co-stimulation factors CD86 and CD80. Naive CD4(+) T cells expressed high levels of CD25 and forkhead box P3 (Foxp3) after incubation with rapamycin-treated and HSP60-loaded DC and displayed moderate antigen-specific, IL-10-independent inhibitory function in vitro. After adoptive transfer, HSP60-specific CD4(+)CD25(high) T cells inhibited the formation of plaques, while ovalbumin-specific cells did not. These findings suggest that RPM-treated DC can induce antigen-specific CD4(+)CD25(high) Treg cells that have inhibitory activity in vitro and prevent the development of plaques in vivo.     

Current understanding of Th2 cell differentiation and function

Helper T cell (Th) has been identified as a critical immune cell for regulating immune response since 1980s. The type 2 helper T cell (Th2), characterized by the production of interleukin-4 (IL-4), IL-5 and IL-13, plays a critical role in immune response against helminths invading cutaneous or mucosal sites. It also has a functional role in the pathophysiology of allergic diseases such as asthma and allergic diarrhea. Currently, most studies have shed light on Th2 cell function and behavior in specific diseases, such as asthma and helminthes inflammation, but not on Th2 cell itself and its differentiation. Based on different cytokines and specific behavior in recent research, Th2 cell is also regarded as new subtypes of T cell, such as IL-9 secreting T cell (Th9) and CXCR5⁺ T follicular helper cells. Here, we will discuss the latest view of Th2 cell towards their function and the involvement of Th2 cell in diseases.     

The role of a heat shock protein from V. cholerae 0139 in the gut immune response

An immunodominant heat shock protein (Hsp 24) was purified from Vibrio cholerae O139 at 42 degrees C and used as an immunomodulator for studying the gut immune response. T cell clone and T cell line specific for the Hsp 24 were generated from the lymphocytes of lamina propria and intra-epithelial lymphocytes of mice orally infected with V. cholerae O139, respectively. The T cell clone was TCR alphabeta(+), CD4(+) and appeared to play an important role in the functioning of gut B-lymphocytes. The T cell line had heterogenous population of CD8+ and CD4+ cells, most of which were found to be TCR alphabeta(+) and a minor population was TCR gammadelta(+). The lymphokine profile of T cell line showed IFN-gamma to be the most abundant lymphokine followed by IL-2 and IL-4. The possible involvement of alternative pathway of activation for T cell clone was also addressed in this study. The splenocytes showed an up-regulation of their CD2 receptor expression on stimulation with the Hsp-24. The pattern of lymphokines released by splenocytes stimulated with the Hsp-24 showed no particular cell type to be responsible for mounting immune response. Thus, there is involvement of both, mucosal and peripheral arm of the immune system.