外周血调节性T细胞检测在再生障碍性贫血诊断中的价值

目的 分析外周血调节性T细胞检测在再生障碍性贫血(再障)诊断中的价值.方法 选择2018年4月至2020年3月于我院就诊的31再障患儿为研究对象,根据再障类型将其分成非重型再障组(21例)和重型再障组(10例);另选20例健康儿童为对照组.比较三组的外周血调节性T细胞水平、Foxp3 mRNA表达水平及TGF-β1水平...     

Foxp3磷酸化通过调控调节性T细胞功能对类风湿关节炎大鼠TNF-α抑制状态影响的分子机制

目的探究Foxp3磷酸化通过调节性T细胞功能改善类风湿关节炎大鼠肿瘤坏死因子-α(TNF-α)抑制状态的分子机制。方法建立类风湿关节炎大鼠模型,分组为正常组(无特殊处理)、模型组(类风湿关节炎模型)和实验组(类风湿关节炎模型+尾静脉注射TNF-α阻滞剂进行治疗)。酶联免疫吸附(ELISA)检测炎症因子白介素10(IL-10)、白介素17(IL-17)和转化生长因子-β(TGF-β)水平;流式细胞术检测T细胞阳性率;Western Blot检测TNF-α表达以及试剂盒检测Foxp3磷酸酶活性。结果与正常组相比,模型组IL-10、TGF-β水平显著降低,IL-17水平显著升高(P<0.05);与模型组相比,实验组IL-10、TGF-β的水平显著升高,IL-17的水平显著降低(P<0.05)。与正常组相比,模型组CD4^+CD25^+T细胞和CD4^+CD25^+Foxp3^+T细胞检测阳性率均显著降低(P<0.05);与模型组相比,实验组以上指标检测比率均显著增加(P<0.05);与正常组相比,模型组的TNF-α蛋白相对表达量显著增加(P<0.05);与模型组相比,实验组TNF-α蛋白的相对表达量显著降低(P<0.05)。与正常组相比,模型组的Foxp3磷酸酶活性显著降低(P<0.05);与模型组相比,实验组Foxp3磷酸酶活性显著升高(P<0.05)。结论通过尾静脉注射TNF-α阻滞剂治疗后,大鼠炎症反应水平、TNF-α蛋白表达及FOXP^3磷酸酶活性均降低,机制可能是Foxp3磷酸化通过调控调节性T细胞数量及炎症因子的变化参与对类风湿关节炎大鼠抑制状态,从而一定程度缓解类风湿关节炎不良症状。     

Adoptive transfer of ex vivo expanded regulatory T cells improves immune cell engraftment and therapy-refractory chronic GvHD

1. Download : Download high-res image (165KB)
2. Download : Download full-size image

     

Olaparib Suppresses MDSC Recruitment via SDF1α/CXCR4 Axis to Improve the Anti-tumor Efficacy of CAR-T Cells on Breast Cancer in Mice

1. Download : Download high-res image (126KB)
2. Download : Download full-size image

     

Dichotomous effects of cellular expression of STAT3 on tumor growth of HNSCC

1. Download : Download high-res image (107KB)
2. Download : Download full-size image

     

Gene Therapy-Induced Antigen-Specific Tregs Inhibit Neuro-inflammation and Reverse Disease in a Mouse Model of Multiple Sclerosis

1. Download high-res image (331KB)
2. Download full-size image

     

原因不明复发性流产病理妊娠患者外周血CD4+CD25+Treg、Foxp3mRNA的表达

目的探讨原因不明复发性流产(URSA)病理妊娠患者外周血CD4+CD25+调节性T细胞(Treg)及叉状头/翅膀状螺旋转录因子(Foxp3)mRNA的表达。方法采用流式细胞术测外周血CD4+CD25+Treg,半定量、实时荧光定量PCR分析外周血单个核细胞Foxp3转录水平;检测70例原因不明复发性流产史妇女(URSA未孕组)、20例病理妊娠妇女(URSA病理妊娠组)、22例正常妊娠妇女组(正常妊娠组)、20例正常非孕妇女组(对照组)外周血中CD4+CD25+Treg、Foxp3 mRNA的表达情况。采用酶联免疫吸附法检测血清白细胞介素-10(IL-10)水平。结果 URSA未孕组外周血CD4+CD25+Treg、Foxp3 mRNA、IL-10比例明显低于正常非孕妇女组,两组比较,差异均有统计学意义(t分别=3.61、4.18、2.71,P均<0.05);URSA病理妊娠组外周血中CD4+CD25+Treg、Foxp3 mRNA、IL-10低于正常妊娠妇女组,两组比较,差异均有统计学意义(t分别=3.79、12.56、4.42,P均<0.05)。结论外周血CD4+CD25+Treg、Foxp3 mRNA和IL-10表达水平降低可能与URSA病理妊娠患者的发病有关。     

Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance

To identify endocytic receptors that allow dendritic cells (DCs) to capture and present antigens on major histocompatibility complex (MHC) class I products in vivo, we evaluated DEC-205, which is abundant on DCs in lymphoid tissues. Ovalbumin (OVA) protein, when chemically coupled to monoclonal alphaDEC-205 antibody, was presented by CD11c+ lymph node DCs, but not by CD11c- cells, to OVA-specific, CD4+ and CD8+ T cells. Receptor-mediated presentation was at least 400 times more efficient than unconjugated OVA and, for MHC class I, the DCs had to express transporter of antigenic peptides (TAP) transporters. When alphaDEC-205:OVA was injected subcutaneously, OVA protein was identified over a 4-48 h period in DCs, primarily in the lymph nodes draining the injection site. In vivo, the OVA protein was selectively presented by DCs to TCR transgenic CD8+ cells, again at least 400 times more effectively than soluble OVA and in a TAP-dependent fashion. Targeting of alphaDEC-205:OVA to DCs in the steady state initially induced 4-7 cycles of T cell division, but the T cells were then deleted and the mice became specifically unresponsive to rechallenge with OVA in complete Freund's adjuvant. In contrast, simultaneous delivery of a DC maturation stimulus via CD40, together with alphaDEC-205:OVA, induced strong immunity. The CD8+ T cells responding in the presence of agonistic alphaCD40 antibody produced large amounts of interleukin 2 and interferon gamma, acquired cytolytic function in vivo, emigrated in large numbers to the lung, and responded vigorously to OVA rechallenge. Therefore, DEC-205 provides an efficient receptor-based mechanism for DCs to process proteins for MHC class I presentation in vivo, leading to tolerance in the steady state and immunity after DC maturation.     

不同分期老年 COPD 患者 Treg 细胞比例及炎性因子水平的研究

目的：观察和分析不同分期老年慢性阻塞性肺疾病（COPD）患者 Treg 细胞比例及炎性因子水平的变化情况。方法选取老年 COPD 患者100例,将处于急性加重期的患者纳入急性组,将处于稳定期的患者纳入稳定组,两组分别纳入42例和58例,选取健康人50例作为对照组。对三组研究对象外周血中的 CD4＋ Foxp3＋ Treg 细胞的比例、CD4＋ CD25＋ Treg 细胞的比例以及肿瘤坏死因子-α（TNF-α）、白细胞介素-8（IL-8）、白细胞介素-6（IL-6）、白细胞介素-1（IL-1）的水平进行检测和比较。结果急性组患者的 CD4＋ Foxp3＋ Treg 细胞比例显著高于对照组（P ＜0．05）,对照组研究对象的 CD4＋ Foxp3＋ Treg 细胞比例显著高于稳定组（P ＜0．05）;急性组患者的 TNF-α、IL-8、IL-6、IL-1水平均显著高于稳定组（P ＜0．05）,稳定组患者的上述指标均显著高于对照组（P ＜0．05）。结论老年 COPD 患者在急性加重期表现为 Treg 细胞比例的异常升高和炎性因子水平的大幅度上升,这可能是造成急性加重期 COPD 患者感染和损伤程度加重的原因之一,稳定期老年 COPD 患者仍存在过度炎症反应的现象,但程度相对较低,并出现了 Treg细胞比例下降的机体自我保护现象。     

Development of new strategies to prevent type 1 diabetes: the role of animal models

Type 1 diabetes is an immune‐mediated disease typically preceded by a long preclinical stage during which a growing number of islet‐cell‐specific autoantibodies appear in the serum. Although antigen‐specific T lymphocytes and cytokines rather than these autoantibodies are the likely executors of β‐cell‐destruction, these autoantibodies reflect the existence of autoimmunity that targets islet β‐cells. Abrogation of this autoimmunity during the preclinical stage would be the key to the prevention of type 1 diabetes. However, the quest of protecting islet‐cells from the immune attack requires detailed knowledge of mechanisms that control islet‐inflammation and β‐cell‐destruction, and of mechanisms that control immune tolerance to peripheral self‐antigens in general. This knowledge can only be obtained through further innovative research in experimental animal models. In this review, we will first examine how research in non‐obese diabetic mice has already led to promising new strategies of diabetes prevention now being tested in human clinical trials. Thereafter, we will discuss how recent advances in understanding the mechanisms that control immune response to peripheral self‐antigens such as β‐cell antigens may help to develop even more selective and effective strategies to prevent diabetes in the future.     

流式细胞术检测RA患者外周血CD4^＋CD25^＋FOXP3^＋ Treg细胞及其GITR表达

目的研究FOXP3和糖皮质激素诱导的肿瘤坏死因子受体(GITR)在类风湿关节炎(RA)患者外周血Treg细胞的表达并探讨其临床意义。方法用五色流式细胞术(FCM)检测40例健康体检者、61例RA患者外周血CD4 CD25 FOXP3 调节性T细胞(Treg)及其中GITR的表达情况。结果RA患者组FOXP3的平均荧光强度(MFI)低于健康对照组(P<0.05),CD4 CD25 FOXP3 Treg占CD4 T细胞的比例、CD4 CD25 FOXP3 Treg中GITR的表达率、GITR MFI和健康对照组相比无统计学差异(P>0.05);活动期RA患者的FOXP3 MFI和GITR MFI均显著低于非活动期组(P<0.01和P=0.032),CD4 CD25 FOXP3 Treg占CD4 T细胞中的比例、CD4 CD25 FOXP3 Treg中GITR的表达率与非活动期组相比无统计学差异(P>0.05)。结论RA患者的FOXP3表达低下,活动期组的FOXP3表达低于非活动期组,为其作为RA病情变化的判断指标提供进一步的证据。     

CD4+CD25+ regulatory T cell therapy for the induction of donor-specific clinical transplantation tolerance

Naturally occurring CD4⁺CD25⁺ regulatory T cells (Tregs) have been shown to play a key role in the control of autoimmunity. Interestingly, they are also capable of mediating transplantation tolerance and they can have indirect allospecificity for donor antigens. An increasing body of evidence in experimental studies has indicated that adoptive transfer of in vitro expanded CD4⁺CD25⁺ Tregs with indirect antidonor allospecificity can induce long-term donor-specific transplantation tolerance. Thus, adoptive cell therapy using patient-specific CD4⁺CD25⁺ Tregs as individualised medicine to promote clinical transplantation tolerance is promising.     

Current and future therapeutic strategies for functional repair of spinal cord injury

Spinal cord injury (SCI) is one of the major disabilities dealt with in clinical rehabilitation settings and is multifactorial in that the patients suffer from motor and sensory impairments as well as many other complications throughout their lifetimes. Many clinical trials have been documented during the last two decades to restore damaged spinal cords. However, only a few pharmacological therapies used in clinical settings which still have only limited effects on the regeneration and functional recovery. This review presents recent clinical trials and recent advances in the development of strategies to restore locomotion after SCI. Several approaches toward functional recovery in SCI succeeded in acute and subacute phases in animal models.However, effective strategies against chronic phase of SCI have not been established yet. The strategy aiming to inhibit single molecule sometimes shows controversial results. In SCI, a lot of players participate in motor and sensory dysfunctions. Therefore, sufficient functional recovery may be achieved by regulating multiple targets. Regrowth of tracts connecting the brain and spinal cord, and axonal sprouting of propriospinal interneurons are fundamentally important for neuronal network working. In addition, remyelination, protection of neuronal death, inhibition of inflammation, and upregulation of beneficial influence of astrocytes are also quite crucial to supporting the axonal refining. Combination of several strategies might be useful as practical therapy. Several compounds such as a Sema3A inhibitor, estrogen, withanoside IV and their relating compounds or other neurotrophic factor-mimicking agents may be candidates for useful SCI therapeutic drugs since those have multi-effects on damaged spinal cord.