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1.
Abstract: T lymphocytes show a special affinity for the skin. Although the roles played by the CD4+ population of T lymphocytes in immunodermatology were so far actively investigated, much less is known about the roles played in the skin by CD8+ cytolytic T lymphocytes (CTL). The activity of CD8+ CTL in the immunodermatological context, however, is likely to be most important; the immuno-biology itself of CD8+ CTL, moreover, although far from being fully understood, shows intriguing characteristics. Immunophenotype, function and cytokine profile of CD8+ CTL are overviewed in the first section of this review. Phenotypically, not only CD8+ CTL can be subdivided into CD8+ CD28+ CD11b+ and CD8+ CD28- CD11b+ subsets, but also an up-to-now undetected CD8+ CD28- CD11b- subset does exist. Functionally, not only “cytotoxic” but even “suppressor” subpopulations have been shown to exert cytolytic capabilities indeed, and “suppression” itself may be due to such a lytic capacity. According to cytokine synthesis, CD8+ CTL can be split into Tc1 and Tc2 subsets, each able to influence specific patterns of immune responses. The impact of CD8+ CTL in immunodermatology, overviewed in the second section of the current review, is crucial. The pathophysiology of inflammatory dermatoses is deeply influenced by the activity of CD8+ CTL: e.g., CD8+ CTL within psoriateic epidermis are possibly associated to the persistence of psoriatic lesions not undergoing resolution; on the other hand, in late lesions of lichen planus CD8+ CTL predominate, thus explaining presumably both the cytolytic attack against keratinocytes and the modulation of the inflammatory reaction up to the final resolution of the lesions; Tc1 cells are decreased in atopic dermatitis, and such a decrease can account both for IgE overproduction and for development of infections. Finally, CD8+ CTL can sustain against cutaneous viruses/tumors cytolytic immune responses not only of secondary but even of primary type, i.e. induced by Langerhans cells/dendritic cells either transfected or pulsed with skin virus/tumor-associated antigens, thus allowing the production of vaccines against cutaneous viral/neoplastic diseases.  相似文献   

2.
Abstract Involvement of T-lymphocytes in the pathogenesis of psoriasis and atopic dermatitis is well established. The question arises as to whether not only tissue infiltrating but also circulating T-lymphocytes are involved in the disease process. Therefore we sought to determine whether T-lymphocytes from patients with psoriasis and atopic dermatitis show abnormal biological behavior to the proinflammatory chemokine interleukin 8 (IL-8) in vitro as studied by their chemotactic activity. In addition, the expression of T-cell activation markers such as HLA-DR and interleukin 2 receptor (IL-2R) were analysed with FACS-technique. In all, 25 patients with psoriasis (13 patients with severe psoriasis and 12 patients with mild psoriasis) and 11 patients with atopic dermatitis were investigated. For comparison, T-lymphocytes from 14 healthy controls were tested equally. The results show that T-cell chemotactic responses to IL-8 were significantly decreased in patients with severe psoriasis as compared to healthy controls. T-cells from patients with atopic dermatitis demonstrated an even more pronounced decrease in chemotactic response as compared to T-cells from psoriasis patients or healthy controls. In contrast, increased expression of activation markers HLA-DR and IL-2R were demonstrated in circulating T-cells from patients with severe psoriasis and atopic dermatitis in comparison to healthy controls. It can be concluded that circulating T-cells in patients with severe psoriasis and atopic dermatitis show a decreased in vitro chemotactic response to IL-8. Furthermore, the in vivo phenotypic activation state of T-lymphocytes in these patients seemed to be associated with their decreased in vitro functional capacity.  相似文献   

3.
目的研究进展期寻常型银屑病患者外周血CD4+CD25+和CD8+CD25+调节性T细胞的数量变化及其在银屑病免疫病理学发病机制中的作用。方法应用流式细胞术对进展期寻常型银屑病患者外周血CD4+CD25+和CD8+CD25+调节性T细胞进行检测。结果进展期寻常型银屑病外周血CD4+CD25+细胞及CD8+CD25+调节性T细胞数量与正常对照组相比,均显著降低(P<0.05,P<0.005),而CD4+CD25+/CD8+CD25+比值无显著性差异(P>0.05)。结论寻常型银屑病的发病与CD4+CD25+和CD8+CD25+调节性T细胞的同步降低有关,与二者的比值无关。  相似文献   

4.
Background  The involvement of oxidative stress in the pathogenesis of various skin disorders has been suggested for decades. However, few clinical studies have assessed oxidative stress in skin diseases. The easiest and least invasive method to assess oxidative stress in patients may be the measurement of oxidation products in urine.
Objective  This study aims to assess oxidative stress in psoriasis and atopic dermatitis patients.
Methods  Urine samples were collected from 29 psoriasis patients (25 males and 4 females), 21 atopic dermatitis patients (14 males and 7 females) and 20 healthy controls (16 males and 4 females). The severity and extent of psoriasis and atopic dermatitis was assessed by their area and severity index. We measured nitrate as a metabolite of nitric oxide, malondialdehyde as a major lipid oxidation product, and 8-hydroxydeoxyguanosine (8-OHdG) as a DNA oxidation marker.
Results  Urinary nitrate and 8-OHdG levels, but not malondialdehyde, were significantly higher in psoriasis patients than those in healthy controls. On the contrary, only urinary nitrate level was significantly higher in atopic dermatitis patients than those in healthy controls. The severity and extent of both psoriasis and atopic dermatitis significantly correlated with urinary nitrate level and malondialdehyde level, but it did not correlate with urinary 8-OHdG level.
Conclusions  Measurement of these three urinary oxidative products is non-invasive. Above all, measurement of urinary nitrate may be most useful in the clinical assessment of oxidative stress in both psoriasis and atopic dermatitis patients. There is a possibility that urinary 8-OHdG level may indicate the different pathogenesis between psoriasis and atopic dermatitis.  相似文献   

5.
目的:检测寻常型银屑病患者外周血髓系树突状细胞(mDCs)表面整合素相关蛋白(CD47)的表达水平。方法:流式细胞仪检测寻常型银屑病患者和健康对照者外周血mDCs表面CD47及CD4+调节性T细胞(Treg)表达水平;Luminex液相芯片技术检测上清液IL-23、IL-17和TNF-α浓度。结果:共检测46例患者和46名健康对照,患者组mDCs细胞CD47表达水平为32.8低于对照组的63.6,差异有统计学意义(P<0.05)。患者组mDCs细胞CD47表达水平与银屑病皮损面积和严重程度指数(PASI)负相关(r=-0.651, P<0.05);患者组Treg细胞比例显著低于对照组,差异具有统计学意义(P<0.05);IL-23、IL-17和TNF-α浓度显著高于对照组,差异具有统计学意义(P<0.05)。结论:银屑病外周血mDCs表面CD47及Treg细胞表达下降。  相似文献   

6.
7.
目的:检测外周血中CD4~+CD25~+调节性T细胞(简称Treg细胞)与Th17细胞在寻常型银屑病(PV)中的表达。方法:34例寻常型银屑病患者,18例正常人作为对照。采用流式细胞术检测外周血中Treg细胞、FOXP3~+Treg细胞及Th17细胞的表达水平。结果:PV患者外周血中Treg细胞比例和FOXP3~+Treg细胞比例分别为(3.68±1.22)%和(0.53±0.19)%,低于正常对照组的(6.63±1.00)%和(0.76±0.14)%(P0.05)。Th17细胞比例为(2.20±0.78)%,高于正常对照组的(0.65±0.22)%(P0.05)。PV患者外周血中Treg细胞的表达与FOXP3~+Treg细胞的表达呈正相关(r=0.563,P0.05),而Treg细胞的表达与Th17细胞的表达呈负相关(r=-0.522,P0.05);Treg细胞和Th17细胞二者与PASI评分无相关性,与病程亦无相关性。结论:Treg细胞表达的减少及Th17细胞应答的增强,可能是导致PV免疫失衡的重要原因。  相似文献   

8.
银屑病和特应性皮炎是常见的以T细胞介导免疫炎症和角质形成细胞异常分化为特征的炎症性疾病.两种疾病在免疫发病机制、临床特征、组织病理、共患病和治疗方法方面有很多共性,但也存在差异.两种疾病的相似性为表皮角质形成细胞对T细胞产生的细胞因子发生异常反应,其增殖和分化发生改变,这也是两种疾病表型的主要原因.但两种疾病的T细胞极...  相似文献   

9.
The role of T cells in the pathogenesis of psoriasis is widely acknowledged. However, key aspects of their precise function in the disease as well as the relative pathogenic contribution of T-cell subsets are still unknown. T-cell clones have been isolated from psoriatic plaques but a study of conditions affecting the isolation and expansion of T-cell clones from psoriatic skin has not been reported to date. Here, we observe a correlation of disease activity with the frequency of the CD3(+)CD8(+)CD25(+) subset. We show that prolonged in vitro culture changes the phenotypic subset distribution of T-cell lines derived from psoriatic skin and that T-cell clones can be isolated by sorting of CD25(+) cells emigrated from skin fragments after 7 days. We evaluate various conditions affecting expansion of psoriatic T-cell clones in vitro and show that blocking apoptosis can facilitate proliferation of activated T-cell clones in vitro. Our results indicate a prominent role of the CD8(+)CD25(+) T-cell subset in disease pathogenesis and should be useful in the design of experiments aiming at a systematic analysis of the specificity of clones present in psoriatic plaques.  相似文献   

10.
目的:检测寻常性银屑病患者血清中白细胞介素(IL)-26的表达量,并分析其对疾病严重程度的影响.方法:选取2017年12月-2019年1月来山西医科大学第一附属医院就诊的寻常性银屑病患者84例作为观察组,其中进展期患者40例,静止期患者44例;选择同期在该院进行健康体检的志愿者40例作为对照组.采用流式细胞术检测2组患...  相似文献   

11.
BACKGROUND: A number of studies exist demonstrating the increased expression of type 2 cytokines and decreased capacity to produce interferon-gamma (IFN-gamma) in peripheral blood mononuclear cells (PBMCs) of patients with atopic dermatitis (AD). OBJECTIVES: To clarify the results of recent studies concerning the role of interleukin (IL)-4 and IL-13 in PBMCs of AD patients, we analysed the activation status of lymphocyte subpopulations. METHODS: We measured the intracellular expression and serum levels of certain type 1 and type 2 cytokines, using cell surface and intracellular cytokine staining, flow cytometry and enzyme-linked immunosorbent assay techniques. RESULTS: The frequency of IL-10 and IL-13 producing CD4+ and CD8+ T cells was significantly higher in patients with AD, while the frequency of IFN-gamma secreting helper and cytotoxic T cells was significantly lower in patients with AD than in control subjects. The serum levels of IL-10 and IL-13 were also significantly increased. There were no significant differences observed between the experimental groups in the frequency of IL-4 producing CD4+ and CD8+ cells. CONCLUSIONS: This study demonstrates a type 2 cytokine production in the CD4+ and CD8+ T cells of AD patients, which is characterized by an elevated IL-13, but not by IL-4 secretion, and by an increased level of the immunoregulatory IL-10, which can contribute to a decrease in IFN-gamma expression.  相似文献   

12.
 

目的 研究PI3K和Notch信号途径在寻常型银屑病患者外周静脉血CD4+ T细胞增殖、活化中的影响。方法 采集28例寻常型银屑病患者和28例健康对照外周静脉血,采用免疫磁珠法分选外周血CD4+ T细胞。将寻常型银屑病患者外周血CD4+ T细胞分为4组:空白对照组,10 μmol/L PI3K阻滞剂组(LY294002组),25 μmol/L Notch阻滞剂组(DAPT组),10 μmol/L LY294002+25 μmol/L DAPT组(LY294002+DAPT组)。均分别用植物血凝素(PHA)10 μg/mL和IL-2 1 000 U/mL刺激增殖6 h,采用FCM检测CD4+ T细胞内的CyclinA、Cyclin D1及P27kipl细胞周期蛋白水平,逆转录-聚合酶链反应(RT-PCR)检测Cyclin A、Cyclin D1及P27kipl mRNA水平,并对数据进行统计学处理。结果 CD4+ T细胞经免疫磁珠法分选后纯度为(90.00±3.90)%,CD4+ T细胞培养存活百分率达(92.50±4.60)%。寻常型银屑病患者外周血CD4+ T细胞Cyclin A、Cyclin D1水平分别为(27.60±3.80)%、(14.70±3.20)%,mRNA水平分别为0.56±0.14、1.37±0.39,与健康对照组(13.50±3.70)%、(7.80±2.00)%和(0.31±0.12)、(0.93±0.35)比较均明显升高,差异有统计学意义(P分别为0.002、0.037和0.008、0.043)。寻常型银屑病患者外周血CD4+ T细胞P27kipl蛋白和mRNA分别为(23.50±3.60)%和(0.17±0.02),均低于健康对照组的(36.80±5.60)%和(0.33±0.05),差异有统计学意义(P分别为0.007、0.001)。与空白对照组CD4+ T细胞Cyclin D1蛋白和mRNA表达[分别为(12.30±3.50)%和(1.74±0..39)]比较,LY294002组、DAPT组、LY294002+DAPT组表达均下降,分别为(7.20±3.10)%、(8.20±2.50)%、(4.30±1.50)%和(1.11±0.29)、(1.26±0.28)、(0.63±0.20),差异均有统计学意义(均P<0.05)。与空白对照组CD4+ T细胞P27kipl蛋白[(21.80±3.20)%]比较,LY294002组、DAPT组、LY294002+DAPT组蛋白水平均升高,分别为(30.90±5.10)%、(27.60±5.20)%、(43.90±3.00)%,差异均有统计学意义(P分别为0.005、0.006、0.001);与空白对照组CD4+ T细胞P27kipl mRNA(0.15±0.08)比较,LY294002组、DAPT组、LY294002+DAPT组水平均上升,分别为(0.37±0.07)、(0.62±0.09)、(0.99±0.21),差异均有统计学意义(P分别为0.018、0.002、0.003)。空白对照组、LY294002组、DAPT组、LY294002+DAPT组组间CD4+ T细胞Cyclin A蛋白和mRNA表达无显著性差异(均P>0.05)。结论 PI3K与Notch信号途径可协同增强CD4+ T细胞内正向调节蛋白Cyclin D1水平升高及负向调节蛋白P27kipl水平下降,提示PI3K和Notch信号途径对寻常型银屑病患者外周血CD4+ T细胞的增殖、活化起着协同调控作用。

  相似文献   

13.
【摘要】 目的 探讨特应性皮炎(AD)患者外周血CD8+ T细胞皮肤归巢及杀伤功能相关蛋白的表达。 方法 15例AD患者和14例健康人,用流式细胞仪,检测外周血CD8+ T细胞、表达皮肤淋巴细胞相关抗原的CD8+ T细胞(CLA+CD8+ T细胞)的比例。 结果 CD8+ T细胞比例在AD组和对照组之间差异无统计学意义(P > 0.05);CD8+ T细胞穿孔素、颗粒酶B和FasL的表达在两组间差异亦无统计学意义(均P > 0.05)。CLA+CD8+ T细胞比例在AD组(3.80% ± 1.46%)高于健康对照组(2.18% ± 0.85%)(t = 3.636,P < 0.01),AD组CLA+CD8+ T细胞比例与SCORAD(SCORing of Atopic Dermatitis)评分呈正相关(r = 0.565,P < 0.05);CCR4在CD8+ T细胞表达在AD组(13.86% ± 4.42%)高于健康对照组(9.50% ± 2.14%)(t = 3.738,P < 0.01),而CCR10和CXCR6的表达在两组间差异均无统计学意义(P > 0.05)。CLA+CD8+ T细胞穿孔素的表达在AD组(74.27% ± 15.94%)高于健康对照组(57.20% ± 14.64%)(t = 2.998,P < 0.01),颗粒酶B的表达在AD组(70.90% ± 13.85%)也高于健康对照组(56.41% ± 11.00%)(t = 3.104,P < 0.01),而FasL的表达在两组间差异无统计学意义(P > 0.05)。CLA+CD8+ T细胞CCR4、CCR10和CXCR6的表达在AD组与对照组间差异无统计学意义(均P > 0.05)。 结论 AD患者外周血CLA+CD8+ T细胞数量增加,杀伤功能相关蛋白穿孔素、颗粒酶B的表达增强,可能参与了AD的发病。  相似文献   

14.
BACKGROUND: It has been established recently that CD4+CD25+ regulatory T cells (Tregs) play an important role in controlling various immune responses. Immunosuppressive drugs are often used to treat immune dysregulation but are frequently associated with undesirable side-effects. OBJECTIVES: We examined the suppressive capacity of circulating Tregs in patients with atopic dermatitis (AD). Combined effects of Tregs and tacrolimus on the inhibition of T-cell proliferation in vitro were also assessed. METHODS: CD4+CD25+ and CD4+CD25- T cells were isolated from peripheral blood mononuclear cells using immunomagnetic beads. CD4+CD25- T cells were stimulated with purified protein derivative (PPD) or house dust mite allergen (Der p1) for 6 or 7 days, respectively. A dose range of tacrolimus and CD4+CD25+ T cells were added separately, or together. Proliferation was measured by (3)H-thymidine incorporation. RESULTS: CD4+CD25+ T cells from normal controls and patients with AD are anergic and inhibit the proliferation of CD4+CD25- T cells in response to PPD and Der p1 in vitro in a dose-dependent manner. Addition of tacrolimus and Tregs together showed significantly stronger inhibition of proliferation than either on their own. This was true for both antigens and both in normal controls and in patients with AD. CONCLUSIONS: CD4+CD25+ T cells in patients with AD have normal suppressive activity compared with healthy controls. Tregs and tacrolimus have additive effects on the inhibition of proliferation in response to PPD and Der p1.  相似文献   

15.
目的:明确广谱半胱氨酸天冬氨酸蛋白酶(caspase)抑制剂对特应性皮炎(AD)患者外周血CD4+T细胞亚群分泌细胞因子的影响。方法:广谱caspase抑制剂Z-VAD-FMK与30例AD患者外周血单一核细胞(PBMCs)体外共培养后,PBMCs分为3组,分别加入Z-VAD-FMK溶液、地塞米松溶液和PBS溶液。流式细胞仪检测CD4+T细胞亚群;ELISA方法检测上清液中IFN-γ、IL-4、IL-17的浓度。结果:IFN-γ、IL-4、IL-17水平在PBS溶液组高于Z-VAD-FMK组,差异均有统计学意义(均P<0.01),在Z-VAD-FMK组与地塞米松组间比较,均无统计学意义(均P>0.05)。结论:广谱caspase抑制剂Z-VAD-FMK可抑制AD患者PBMC中CD4+T细胞Th1、Th2、Th17分泌相关细胞因子。  相似文献   

16.
To determine the proportion of T-helper cell subsets in the peripheral blood we studied 16 patients with mild, moderate and severe atopic dermatitis. Lymphocytes were isolated from heparinized peripheral blood and analysed by two-colour flow cytometry. Patients with severe atopic dermatitis had a decreased CD4+CD29+CD4+CD45RA+ ratio (p<0.01). We found a decreased absolute number of CD4+CD29+ cells (p<0.05) and an increased absolute number of CD4+CD45RA+ cells (p<0.05) in the peripheral blood. No significant changes in the CD4+CD29+CD4+CD45RA+ ratio were found in the peripheral blood of patients with clinically mild or moderate atopic dermatitis.  相似文献   

17.
18.
BACKGROUND: In psoriasis CD4+CD25+ regulatory T cells are functionally deficient. The imbalance between regulatory and effector T-cell functions is important for inducing psoriasis. It is reasonable to speculate that the dysfunctional activity of CD4+CD25+ regulatory cells may originate partly from the abnormal haematopoietic cells determined mainly by genetic background. OBJECTIVES: To test the hypothesis that haematopoietic stem cells are responsible for dysfunctional CD4+CD25+ regulatory cells in psoriasis. METHODS: Bone marrow-derived CD34+ haematopoietic cells from patients with psoriasis (with a family history of psoriasis) and from normal controls were differentiated into T cells in vitro. CD4+CD25+ T cells were isolated by an immunomagnetic bead method, and proliferation activity and capacity for cytokine secretion were determined. Furthermore, the ability of CD4+CD25+ T cells to suppress the proliferative responses of allogeneous peripheral blood CD4+CD25- effector T cells was assessed in vitro. RESULTS: The differentiated CD4+CD25+ T cells of psoriatic origin showed similar characteristics to those of normal volunteers, including proliferation activity and secretion profile of the cytokines interleukin (IL)-2, IL-4, IL-8, IL-10 and interferon (IFN)-gamma. However, proliferation and secretion levels of the cytokines IL-2 and IL-10 for CD4+CD25+ cells of psoriatic CD34+ cell origin were significantly lower than those of normal controls in response to streptococcal superantigen (Strep-A). In particular, CD4+CD25+ T cells differentiated from psoriatic CD34+ cells were functionally insufficient to restrain effector T-cell proliferation. CONCLUSIONS: CD4+CD25+ T cells differentiated in vitro from haematopoietic cells of patients with psoriasis are impaired in regulatory function. The dysfunction of psoriatic CD4+CD25+ T cells may be due to inherent genetic programming passed down from bone marrow-derived haematopoietic cells.  相似文献   

19.
The majority of epidermal CD8+ T cells in chronic plaque psoriasis are activated Tc1 cells producing interferon-gamma and no interleukin-4, a small proportion of which express NK-T receptors. To quantitate their level of cytokine production and characterize them further, CD8+ T cells were isolated from epidermal cell suspensions of lesional biopsies from 24 patients with chronic plaque psoriasis. T-cell lines (TCL) were established by culture of CD8+ T cells with feeders and IL-2 for 11 days and expansion with PHA. Ten TCL were stained for surface markers; 6 were cloned with PHA by limiting dilution. Interferon-gamma, interleukin-4 and interleukin-10 production was measured by ELISA after PMA/anti-CD3 activation of 15 TCL and 39 CD8+ T-cell clones. The 10 TCL stained were CD8alphabeta+ (93.3%), T-cell receptor-alphabeta+ (99.5%), costimulatory molecule CD28+ (90.1%), with a small CD8alphaalpha+ population (2.3%). No NK-T-cell receptor CD158a or CD158b expression was detected, whilst CD94 was expressed on 6.2% of cells in 6/9 TCL. All the TCL and 37/39 CD8+ T-cell clones produced interferon-gamma but no or minimal interleukin-4 or interleukin-10. The TCL produced a wide range of interferon-gamma levels (138 to 15,020 pg/ml). Clones from 3 patients showed low levels (60 to 1,410 pg/ml), from 2 patients high levels (6,105 to 43,040 pg/ml) and from 1 patient a wide range (405 to 36,010 pg/ml) of interferon-gamma production. Thus epidermal CD8+ Tc1 cells in chronic plaque psoriasis produce highly heterogeneous levels of interferon-gamma, which may reflect clinical diversity.  相似文献   

20.
Background It is well known that regulatory T cells (Tregs), identified by their expression of CD4, CD25 and Foxp3, play a crucial role in maintaining peripheral tolerance. Recently, it has been demonstrated that a Treg population resides in normal human skin. However, only a few studies have demonstrated the presence of Foxp3+ Tregs in inflammatory skin disorders. Objectives In this study, we immunohistologically examined the presence of CD4+ CD25+ Foxp3+ Tregs in the lesional skin of psoriasis vulgaris, mycosis fungoides and eczematous dermatitis. Methods We used immunohistochemistry to examine the presence of Foxp3+ Tregs in fixed sections of the lesional skin from 16 patients with psoriasis vulgaris, 17 patients with mycosis fungides and 18 patients with eczematous dermatitis in addition to 10 normal skin samples. Results In normal skin, epidermal and dermal Foxp3+ cells were rare. The psoriasis vulgaris, mycosis fungoides and eczematous dermatitis samples contained substantial numbers of epidermal and dermal CD3+, CD4+ and CD25+ Foxp3+ Tregs. The epidermis contained a higher percentage of CD3+, CD4+ and CD25+ Foxp3+ cells than the dermis. The percentage of Foxp3+ cells among CD3+ or CD4+ cells was significantly lower in eczematous dermatitis than in psoriasis vulgaris or mycosis fungoides, and that of dermal Foxp3+ cells was significantly lower in psoriasis vulgaris than in eczematous dermatitis or mycosis fungoides. Conclusions The lower percentage of epidermal or dermal Foxp3+ cells in eczematous dermatitis or psoriasis vulgaris, respectively, might contribute to their pathogenesis.  相似文献   

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