胫前黏液性水肿发生发展机制的研究进展

在自身免疫性甲状腺疾病背景下,循环自身抗体与成纤维细胞上自身抗原结合,产生IL～16和活化后可调节的正常T细胞表达并可能分泌的因子,趋化吸引CD4+T淋巴细胞.浸润T细胞活化成纤维细胞,分泌IL-6、8和巨噬细胞趋化蛋白-1,吸引炎性细胞浸润,形成血管周围炎.自身抗体、细胞因子与浸润T细胞使成纤维细胞合成过多透明质酸,发生黏液性水肿.局部创伤、感染可能起触发作用.持续大量细胞因子和透明质酸刺激成纤维细胞增殖并分化为肌成纤维细胞,过度合成细胞外基质,真皮纤维化,皮肤硬化.     

胫前黏液性水肿发生发展机制的研究进展

在自身免疫性甲状腺疾病背景下,循环自身抗体与成纤维细胞上自身抗原结合,产生IL～16和活化后可调节的正常T细胞表达并可能分泌的因子,趋化吸引CD4+T淋巴细胞.浸润T细胞活化成纤维细胞,分泌IL-6、8和巨噬细胞趋化蛋白-1,吸引炎性细胞浸润,形成血管周围炎.自身抗体、细胞因子与浸润T细胞使成纤维细胞合成过多透明质酸,发生黏液性水肿.局部创伤、感染可能起触发作用.持续大量细胞因子和透明质酸刺激成纤维细胞增殖并分化为肌成纤维细胞,过度合成细胞外基质,真皮纤维化,皮肤硬化.     

扁平苔藓发病机理的研究进展

本文就T淋巴细胞、郎格罕细胞、角朊细胞及其它一些细胞因子在扁平苔藓发病机制中的作用进行了综述,提出了可能的发病机制,即外来抗原激活郎格罕细胞,使其发生形态和功能的改变并分泌细胞因子,诱导T细胞移入表皮,而后T细胞被激活分泌大量细胞活性因子,这些细胞因子一方面诱导角朊细胞表面表达异常抗原,另一方面进一步吸引T细胞浸润,使T细胞与表面抗原异常的角朊细胞粘附,直接或间接杀伤角朊细胞,从而引起基底细胞的损伤,产生扁平苔藓的病理变化。     

细胞外基质与成纤维细胞的相互作用及其在硬皮病中的意义

细胞外基质与成纤维细胞相互作用的主要表现为:细胞外基质调控成纤维细胞的增殖与分化、对成纤维细胞趋化作用、负反馈抑制成纤维细胞合成胶原。成纤维细胞表面介导细胞外基质-成纤维细胞相互作用的粘附分子主要是整合素β_1、β_3亚族,与多种细胞外基质共同具有的精氨酸-甘氨酸-天冬氨酸序列特异结合。硬皮病中成纤维细胞表面整合素α_1、α_3链表达较正常成纤维细胞明显增强;β_1整合素在皮损血管周围、淋巴样细胞聚集区及胶原束间明显增多;胶原和前胶原肽对成纤维细胞合成胶原的负反馈抑制在硬皮病时消失。细胞因子、转化生长因子-β、干扰素等对细胞外基质-成纤维细胞相互作用有调节作用。     

皮肤光老化机制研究进展

光老化指皮肤由于反复光暴露引起的提前老化,其发生机制涉及细胞内信号转导通路、细胞表面细胞因子和表皮生长因子受体的活化,活性氧族是激发细胞信号转导过程中的重要介质,其结果导致基质金属蛋白酶合成增加,从而使真皮纤维结缔组织过度降解和弹性纤维变性,同时真皮胶原的合成亦减少,角质形成细胞、成纤维细胞及炎症浸润细胞等多种细胞参与光老化过程.     

IL-12家族细胞因子在系统性红斑狼疮发病机制中的研究进展

系统性红斑狼疮(SLE)是一种自身免疫性疾病,其特征是多器官受累和自身抗体的产生.尽管SLE的发病机制仍然未知,但其与T细胞和B细胞过度活跃以及自身抗体产生有关.细胞因子介导的T细胞和B细胞的活化,在包括SLE在内的各种自体免疫疾病的发病机理中都起着至关重要的作用.白介素12(IL-12)家族的异二聚体细胞因子,包括I...     

皮肤光老化机制研究进展

光老化指皮肤由于反复光暴露引起的提前老化,其发生机制涉及细胞内信号转导通路、细胞表面细胞因子和表皮生长因子受体的活化,活性氧族是激发细胞信号转导过程中的重要介质,其结果导致基质金属蛋白酶合成增加,从而使真皮纤维结缔组织过度降解和弹性纤维变性,同时真皮胶原的合成亦减少,角质形成细胞、成纤维细胞及炎症浸润细胞等多种细胞参与光老化过程.     

系统性红斑狼疮患者血清IFN-γ、IL-4、IL-10水平及疾病活动性研究

系统性红斑狼疮(SLE)是一种以B细胞多克隆活化且伴大量自身抗体为特征的自身免疫性疾病.T细胞可调节B细胞的功能且SLE中大多数自身抗体的产生为T细胞依赖性,依据所产生细胞因子的不同Th细胞主要分为Th1、Th2两类[1],人们研究发现SLE中存在着T细胞亚群的异常和细胞因子的异常[2-5],本研究着重检测SLE患者血清IFN-γ(Th1型细胞因子)以及IL-4、IL-10(Th2型细胞因子)的水平,旨在了解其改变情况并初步探讨它们与SLE疾病活动性和肾脏损害的关系,现报告如下.     

辅助性T细胞17和调节性T细胞与皮肤病

辅助性T细胞17和调节性T细胞是近年发现的CD4+T细胞亚群,辅助性T细胞17主要通过其分泌的白介素-17等细胞因子促进中性粒细胞的活化及募集,介导促炎症反应.调节性T细胞主要通过直接接触和分泌抑制性细胞因子等效应机制发挥免疫抑制作用,维持机体自身耐受.两者均参与自身免疫性疾病、感染性疾病及肿瘤等疾病的发生发展.有研究表明,辅助性T细胞17/调节性T细胞平衡异常引起全身或局部免疫应答异常是导致这些疾病的发生发展的重要机制之一.     

自身免疫性大疱性皮肤病细胞免疫机制进展

自身免疫性大疱性皮肤病是一类以皮肤、黏膜红斑和水疱为主要临床表现的皮肤病.体液免疫与细胞免疫均参与发病机制中.其中细胞免疫表现为初始T细胞通过T细胞受体与抗原特异结合后,在一些辅助因素作用下,活化、增殖并分化为效应T细胞,这些细胞表面相关细胞因子通过与B细胞表面相关受体结合,从而激发B细胞产生浆细胞及记忆细胞,进而分化为高亲和力抗体,产生免疫应答.而这些起辅助作用的细胞因子主要有辅助性T细胞、调节性T细胞等相关的细胞因子,这些细胞因子的研究对寻求自身免疫性大疱病的根源及靶向治疗意义重大.     

CD56 highCD16 - NK cell involvement in cutaneous lichen planus

Lichen planus is an inflammatory disease of the skin and mucous membranes characterized by vacuolization of basal keratinocytes associated with a prominent junctional lymphocyte infiltrate which comprises T?lymphocytes, NK cells, myeloid and plasmacytoid dendritic cells. Basal keratinocyte damage is considered as being a consequence of a lymphocytic cytotoxic attack, mostly mediated by perforin+CD8+ T?lymphocytes. NK cells have been described to infiltrate inflamed skin and significantly contribute to the amplification of immune-mediated skin diseases, thanks to their cytotoxic activity and the release of pro-inflammatory cytokines. Here, we investigated the characteristics and functional properties of NK lymphocytes involved in lichen planus. Double staining immunohistochemistry showed a considerable number (6.42 ± 2.2% of the total cellular infiltrate) of CD3-CD56+ cells in early lichen planus lesions, mostly distributed in the papillary dermis and at the epidermal-dermal interface. Skin NK cells isolated from lichen planus lesions belong to the CD56highCD16- subset, are highly positive for perforin and natural cytotoxic receptors NKG2D and NKp44, and, in accordance with their phenotype, are negative for KIRs receptors CD158a and CD158b. Skin CD56highCD16- NK cells display a CCR6+CXCR3+CCR5+ChemR23+ chemokine receptor asset for homing into inflamed skin. In terms of cytokine release, skin CD56highCD16- NK cells are able to secrete IFN-γ, TNF-α and hardly release IL-22, IL-17 and IL-4. Overall, our data propose a pro-inflammatory role of NK lymphocytes in lichen planus.     

Phenotypic and functional outcome of human monocytes or monocyte-derived dendritic cells in a dermal equivalent.

The dermis harbors a true dendritic cell population that could elicit primary allogeneic T cell responses in vitro and contact hypersensitivity reactions in vivo. The origin of dermal dendritic cells remains poorly understood, however. In this study, we analyzed the fate of monocytes or monocyte-derived dendritic cells in a dermal equivalent. Freshly isolated monocytes or monocytes cultured for 6 d with either GM-CSF/IL-4 or GM-CSF/IL-4/TGF-beta 1 (TGF-DC) were seeded in a collagen solution with normal human fibroblasts. The lattices were cultured for 7--14 d in the presence, or absence, of the exogenous cytokines, before phenotypic and functional studies were performed. Supply of exogenous cytokines allows the appearance of typical CD1a(+)/CD14(-)/CD68(low) dendritic cells with significant allostimulatory property, regardless of the cell type incorporated into the lattices. In cytokine-free conditions, monocytes and GM-CSF/IL-4-derived dendritic cells give rise to a CD1a(-)/CD14(+)/CD68(high) monocyte/macrophage population with no allostimulatory property. When incorporated into the lattices in the absence of exogenous cytokines the TGF-DC express few CD68 and FXIIIa. Interestingly, these cells do not all convert into the CD14(+)/CD1a(-) population. Indeed, a small HLA-DR(+)/CD1a(+)/CD14(-) subset was consistently found, which represents about one-third of the HLA-DR(+) cells. Moreover, TGF-DC recovered from the lattices after culture without cytokines do display a significant allostimulatory function. Thus, in the absence of exogenous cytokines, only Langerhans-cell-like dendritic cells can retain the typical dendritic cell features when inserted in a dermal environment. Taken together, these results may provide evidence supporting an epidermal origin of dermal dendritic cells.     

Analysis of the T cells that are potentially involved in autoantibody production in pemphigus vulgaris

Pemphigus vulgaris (PV) is a classical example of an antibody-mediated autoimmune disease of the skin. Direct evidence exists that autoantibodies against the desmosomal adhesion molecule, desmoglein 3 (Dsg3), are critical in the pathogenesis of this disease. The transfer of serum IgG antibodies reactive with Dsg3 into newborn mice induces a bullous skin disease resembling PV. Autoreactive T cell responses to Dsg3 may be critical in the pathogenesis of PV because 1) antibody production generally requires T cell help, 2) the involvement of CD4+ T lymphocytes in PV has been suggested by the strong association with distinct HLA class II alleles, and 3) T cell recognition of epitopes of Dsg3 may be crucial for the initiation and perpetuation of the production of Dsg3-specific autoantibodies by B cells. We and others have identified autoreactive T cells recognizing distinct epitopes of the extracellular portion of Dsg3 in PV patients. These autoreactive CD4+ T cells preferentially produced TH2 cytokines such as IL-4, and IL-10. Autoantibodies of the TH2-dependent IgG4 subtype are preferentially seen in active stages of PV disease, while autoantibodies of the TH1-dependent IgG1 subclass are predominant upon remission of PV. Healthy individuals who carried HLA class II alleles similar or identical to those found to be highly prevalent in PV also developed autoreactive T cell responses to Dsg3. Autoreactive T cells from PV patients produced both TH1 and TH2 cytokines; autoreactive T cells from normals produced TH0 cytokines. These observations suggest that Dsg3-specific T cells may provide targets to eventually modulate the T cell-dependent production of pathogenic autoantibodies in PV.     

A rapid flow cytometric assay to detect CD4+ and CD8+ T-helper (Th) 0, Th1 and Th2 cells in whole blood and its application to study cytokine levels in atopic dermatitis before and after cyclosporin therapy

BACKGROUND: The immune response in atopic dermatitis (AD) is thought to be driven by T-helper (Th) 2 cytokines. Using flow cytometry, higher frequencies of peripheral blood CD4+ and CD8+ T cells producing interleukin (IL)-4 and correspondingly lower frequencies of CD4+ T cells producing interferon (IFN)-gamma have been found in patients with AD compared with healthy controls. It would be of interest to know whether other Th1 and Th2 cytokines such as IL-5, IL-13 and tumour necrosis factor (TNF)-alpha are similarly skewed in patients with AD and whether this immune skewing, detected via a simple blood assay, can be correlated with other clinical measurements or treatments in AD. OBJECTIVES: To use a rapid (4-h) flow cytometric assay to study a wide range of Th1 and Th2 cytokine patterns in peripheral blood lymphocytes from patients with AD, comparing them with non-atopic healthy controls. To correlate cytokine patterns with the degree of eosinophilia observed and in the case of one patient with severe disease, to observe the effect of cyclosporin therapy on peripheral blood cytokine patterns. METHODS: Peripheral blood from eight patients with AD and 23 healthy controls was examined for the frequencies of CD4+ and CD8+ T cells expressing IL-2, IL-4, IL-5, IL-13, IFN-gamma and TNF-alpha using flow cytometry. RESULTS: Significantly higher frequencies of CD4+/IL-4+ (P < 0.005) and CD4+/IL-13+ (P < 0.0001) and lower frequencies of CD4+/IFN-gamma+ (P < 0.002) and CD8+/TNF-alpha+ (P < 0.05) T lymphocytes were found in patients with AD compared with controls. There were significant positive correlations with the increased percentages of CD4+/IL-4+ and CD4+/IL-13+ T lymphocytes and the degree of eosinophilia observed (P < 0.05, P < 0.001) and a negative correlation between the percentage of CD4+/IFN-gamma+ T lymphocytes and eosinophilia (P < 0.05). In one patient examined before and 8 days after cyclosporin therapy, 50% or greater reductions were observed in percentages of peripheral blood CD8+/IL-5+, CD8+/IL-13+, CD4+/IL-4+ and CD4+/IL-5+ T lymphocytes following cyclosporin therapy. A smaller reduction of 15% after cyclosporin therapy was found in percentages of CD4+/IL-13+ T cells. CONCLUSIONS: These data strongly support a Th2 predominance in the peripheral blood of AD. The results suggest that administration of cyclosporin therapy in patients with AD may help to restore the Th2 cytokine imbalance seen in these patients.     

尖锐湿疣患者外周血CD4~+ T细胞细胞因子的检测

目的检测尖锐湿疣(CA)患者外周血CD4+T细胞细胞因子IL-2,IL-12,IFN-γ和IL-4的水平,探讨其在CA发病中的作用。方法应用流式细胞仪对60例CA患者和20例正常对照者外周血CD4+T细胞细胞因子IL-2,IL-12,IFN-γ,IL-4的表达进行了检测。结果CA患者外周血IL-2,IL-12,IFN-γ-CD4+T细胞百分率均显著下降(P<0.001);IL-4-CD4T细胞百分率与正常对照组比较差异无显著性(P>0.05);Th1/Th2比值显著低于正常对照组(P<0.001)。结论CA患者存在Th1/Th2平衡失调,这可能是CA发生、发展的重要原因之一。     

复发性生殖器疱疹患者外周血IL-12与Th1/Th2细胞因子的检测

目的检测复发性生殖器疱疹(RGH)患者不同病期外周血CD4+T细胞内IL-12,IFN-,γIL-4的水平,探讨IL-12,Th1与Th2亚群在疾病中的可能作用。方法应用流式细胞仪对20例发作期、15例恢复期RGH患者和15名健康人外周血CD4+T细胞IL-12,IFN-γ和IL-4进行检测。结果发作期患者外周血IFN-γ+-CD4+T细胞百分率显著低于正常对照组(P<0.05),IL-4+-CD4+T细胞百分率明显高于正常对照组(P<0.01),Th1/Th2比值显著低于正常对照组(P<0.01),同时IL-12+-CD4+T细胞百分率显著降低(P<0.01)。恢复期患者外周血IL-12+-CD4+T细胞百分率仍显著低于正常(P<0.05)。结论RGH患者存在Th1/Th2比例失衡和IL-12水平低下,而后者可能是导致Th1/Th2比例失衡和病情反复发作的重要原因。