银屑病患者角质形成细胞对朗格汉斯细胞免疫刺激功能的影响

为探讨银屑病患者皮损处角质形成细胞对朗格汉斯细胞（LCs）免疫刺激功能的影响，从健康者外周血分离单核细胞，经IL－4＋GM－CSF＋TGF－β1培养5天后分化发育为1Cs,再加入银屑病患者角质形成细胞培养上清继续培养2天，然后通过Leica显微镜观察其形态；通过混合淋巴细胞反应分析其种T的刺激功能。结果显示，以健康人角质形成细胞上清为对照，LCs经银屑病患者角质形成细胞上清培养2天后，拥有不规则突起的细胞明显较正常组增多。同时，其刺激T淋巴细胞增殖的能力也增强。结果表明，银屑病患者角质形成细胞上清培养的LCs表现出较强的免疫刺激功能，并在银屑病相关的免疫反应过程中发挥了重要作用，提示这可能与银屑病患者角质形成细胞表达的某些因子有关。     

Predominant cutaneous infiltration by OKT6- and OKT8-positive cells in a case of Sézary syndrome

Summary Using an immunoperoxidase (skin biopsy) and an immunofluorescence (peripheral blood, bone marrow punctate) technique, and monoclonal antibodies raised against peripheral mature lymphocytes, T helper subsets, T suppressor subsets, and Langerhans cells, we found a predominant dermal infiltration with lymphocytes of the suppressor phenotype and a predominant epidermal infiltration with Langerhans cells in a patient with Sézary syndrome (cutaneous T-cell lymphoma, CTCL). Repeated peripheral blood examinations showed an increased percentage of lymphocytes of the helper phenotype. A bone marrow examination revealed a ratio of suppressor/helper subsets of 1:4. The findings in the skin seem to be inconsistent with most of the results of previous studies in patients with CTCL; the significance of these findings is discussed.This study was partly supported by the Deutsche Forschungsgemeinschaft, Grant no. Lo 285/2-1This work is dedicated to Prof. Th. Nasemann on occasion of his 60th birthday     

Functional characterization of CD4+CD25+ regulatory T cells differentiated in vitro from bone marrow-derived haematopoietic cells of psoriasis patients with a family history of the disorder

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.     

A question of persistence: Langerhans cells and graft‐versus‐host disease

Langerhans cells (LCs) have been scrutinized many times in studies of the pathogenesis of graft‐versus‐host disease (GVHD). As migratory dendritic cells, LCs are capable of direct antigen presentation to cytotoxic T cells. Their self‐renewal capacity has led to speculation that persistent recipient LCs could provide a continuous source of host antigen to donor T cells infused during hematopoietic stem cell transplantation (HSCT). In this issue of Experimental Dermatology, a new study examines at the relationship between recipient LCs and chronic GVHD.     

14例小汗腺螺旋腺瘤临床及病理特征分析

回顾性分析2015-2019年我院皮肤科确诊为小汗腺螺旋腺瘤的14例患者的临床及病理资料,并复习相关文献.结果示14例小汗腺螺旋腺瘤患者中,男5例,女9例,中位发病年龄为40.5岁.10例患者皮疹发生于躯干.皮损形态为皮色、红色、蓝色、浅褐色的皮下包块或结节,且多伴疼痛.14例患者临床首诊均误诊,误诊为表皮囊肿6例、色...     

Two cases of multiple eccrine spiradenoma with linear or localized formation

We report two rare cases of recurrent, multiple eccrine spiradenoma. Both cases presented with extensive lesions comprised of multiple red papules of various sizes and a soft blue-red nodule. The first case was a 30-year-old woman. Her lesions followed a linear arrangement on her chin, and extended down the right side of the neck with spontaneous pain. The second case was a 57-year-old woman with tumors in a localized group on the left occipital region without pain. A search of the literature revealed only 15 reported cases of linear/zosteriform/nevoid multiple eccrine spiradenoma. Both cases were treated by surgical excision. Most of the red papules displayed typical histological features including two cell types: large clear cells with low-density cytoplasm; and small dark cells with high-density cytoplasm. The large soft tumors exhibited a variable histological appearance. In the first case, the cystic tumors displayed an homogeneous structure comprised of eosinophilic material. In the second case, the cystic tumors included abundant interstitial tissue.     

银屑病发病机制中T细胞作用的进展

银屑病是一种Th1细胞介导的自身免疫性皮肤病,近来的研究表明,其他细胞也参与其发病过程,尤其是树突细胞、内皮细胞、Th17细胞及调节性T细胞等,其中T细胞的活化、增殖及分化是发病的主要环节,银屑病特征性的角质形成细胞增殖和异常分化及炎性细胞浸润是继发于T细胞活化后释放的细胞因子.一些黏附分子(E/P选择素等)及皮肤淋巴细胞相关抗原-P选择素糖蛋白配体-1复合体和皮肤淋巴细胞相关抗原-CD43复合体在银屑病发病中也起着一定的作用.     

UV‐induzierte regulatorische T‐Zellen

Regulatory T cells belong to a subset of T lymphocytes which suppress immune reactions in an antigen‐specific fashion. Regulatory T cells play an important role in the prevention of autoimmune diseases. Ultraviolet (UV) radiation suppresses the immune system in antigen‐specific fashion. This effect is mediated by UV‐induced regulatory T cells. UV‐induced regulatory T cells express CD4 and CD25 and upon activation release the immunosuppressive cytokine interleukin‐10. Upon intravenous injection UV‐induced regulatory T cells primarily migrate into the lymph nodes, explaining why they preferentially suppress sensitization. Recently, the development of regulatory T cells was demonstrated in an experimental model of photopheresis. The further characterisation of these cells will determine whether they can be applied in the future therapeutically with the ultimate aim to induce specific immunosuppression.     

The role of cutaneous dendritic cells in the immunopathogenesis of atopic dermatitis

We review the immunology of atopic dermatitis (AD) and focus attention on the role of cutaneous dendritic cells. AD is a complex immune-mediated skin disorder characterized by the recruitment of both CD4+ and CD8+ T cells into the skin. T-helper (Th) 2-type cytokines are dominant in acute AD skin, while both Th1- and Th2-type cytokines are present in chronic AD. Cutaneous dendritic cells, which are present in increased numbers within AD skin, are believed to play a key part in the activation of T cells in the skin. They may also help to determine the pattern of cytokines produced by activated effector T cells.     

IL‐1 signalling determines the fate of skin grafts expressing non‐self protein in keratinocytes

Please cite this paper as: IL‐1 signalling determines the fate of skin grafts expressing non‐self protein in keratinocytes. Experimental Dermatology 2010; 19 : 723–729. Abstract: Although IL‐1 is a known inflammatory cytokine during pathogen infection, the role of IL‐1 in skin graft rejection, particularly where foreign antigen is expressed exclusively in keratinocytes, is less understood. Here, we use a syngeneic skin graft system, where antigens are expressed in epithelial cells via either a keratin 14 or keratin 5 promoter, to explore the role of IL‐1 in graft rejection and induction of epithelial antigen‐specific effector CD8⁺ T‐cell function. Keratin 5 ovalbumin (K5mOVA) transgenic skin grafts destined for rejection demonstrated increased expression of IL‐1β and its receptors compared to K14 HPV16 E7 transgenic grafts that do not reject spontaneously. Rejection of OVA grafts lacking the IL‐1 receptor (IL‐1R1) was delayed and associated with decreased numbers of antigen‐specific CD8 T cells. In contrast, K14E7 grafts survived on immunocompetent, syngeneic recipients with decreased graft levels of IL‐1β and IL‐1R1 and 2. However, in the absence of the IL‐1 receptor antagonist, IL‐1Ra, skin grafts were spontaneously rejected and an E7‐specific CD8 T‐cell response was primed. Thus, expression of the HPV16E7 oncoprotein in epithelial cells prevents IL‐1β‐associated skin graft rejection and induction of antigen‐specific CD8 T‐cell responses. Enhancing IL‐1β signalling, via blocking of the IL‐1 receptor antagonist, may represent an alternative strategy for treatment of HPV16E7‐associated cancers.     

Effect of orally administered aromatic retinoid on murine Langerhans cells

Summary The effect of orally administered aromatic retinoid (Ro 10-9359) on murine epidermal Langerhans cells (LC) was studied in vivo and in vitro. Daily administration of retinoid caused a transient increase in LC density, as determined by staining for Ia antigens, during the first few days of treatment and thereafter a continuing decrease that reached a maximum at 2 weeks. In addition, the morphology and location in the epidermis had been altered. When the treatment was continued to 4 weeks, the density of LC returned to normal. The Ia-antigen-presenting function of epidermal cells to an allo-Ia-reactive cloned T cell line was elevated at all stages of retinoid treatment examined. This elevation did not correlate with the density of histochemically stainable Ia⁺ LC. These findings suggest that orally administered retinoid profoundly alters the functional capacity of Ia⁺ LC.     

Th17细胞／Treg细胞及其失衡在慢性自发性荨麻疹发病机制中的作用

慢性自发性荨麻疹是一种常见的皮肤黏膜变态反应性疾病,以反复出现风团或红斑伴剧烈瘙痒为特征。介导免疫耐受的CD4＋CD25调节性T细胞和介导炎症反应的Thl7细胞是两类不同的CD4q＇细胞。两者数量此消彼长,功能拮抗,调节性T细胞和Thl7细胞数量和功能的平衡对维持免疫稳态起重要作用,失衡可引起免疫应答异常,导致包括慢性自发性荨麻疹在内的自身免疫性疾病的发生。初始CD4＋T细胞的细胞因子对他们之间的关系起到调节作用。     

Immunohistochemical characterization of cellular infiltrates in squamous cell carcinoma and Bowen's disease occurring in one patient.

We investigated populations of the infiltrating cells in Bowen's disease (BD) and squamous cell carcinoma (SCC), both of which arose in the same patient, using the Avidin-Biotin-peroxidase complex method with eight monoclonal antibodies. T lymphocytes were most predominant among infiltrating cells; NK cells, B cells, and monocytes were rarely seen in either BD or SCC. Analysis of subsets of the infiltrating T lymphocytes revealed that the number of suppressor/cytotoxic (s/c) T cells was twice that of helper/inducer (h/i) T cells in BD, while the number of s/c T cells was lower than that of h/i T cells in SCC. The immunohistochemical results in the present case differed from those of predominant infiltration of h/i T cells and of s/c T cells in three other reports of BD and SCC. These results suggest that the population of the cellular infiltrates may be modulated by the nature of tumors and by the immuno-competent state of the hosts.     

In vivo activation of langerhans cells and dendritic epidermal T cells in the elicitation phase of murine contact hypersensitivity

Langerhans cells (LCs) and dendritic epidermal T cells (DETCs) constitute the skin immune system. To demonstrate the kinetics of in vivo activation of murine LCs and DETCs in the elicitation phase of contact hypersensitivity, we measured the cell area positively stained for I-A and gammadeltaT-cell receptor (or Thy-1.2), respectively, under a fluorescence microscope at various time intervals after topical application of dinitrofluorobenzene. The fluorescence-positive area of LCs increased in parallel with that of DETCs at 1 h and 24 h, indicating the biphasic activation of LCs and DETCs. Early activation was hapten-specific and often exhibited close LC-to-DETC apposition. Experiments with in vivo administration of neutralizing anticytokine antibodies revealed that none of interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta were involved in the induction of early activation of LCs and DETCs, while TNF-alpha and IL-1beta mediated late activation of LCs, and IFN-gamma and IL-1beta mediated that of DETCs. Our results indicate that LCs and DETCs are synchronously and biphasically activated in the epidermis during the elicitation phase of contact hypersensitivity and suggest that different mechanisms may control early and late activation.     

小鼠毛囊周期中表皮朗格汉斯细胞及树突状表皮T细胞的变化

目的:观察拔毛诱导的小鼠毛发周期中毛囊间表皮LC及DETC的密度及形态变化,探讨二者与毛囊周期的关系。方法:选用自然休止期C57BL/6小鼠,拔毛诱导毛发进入生长期,应用ABC免疫组化法连续观察毛囊间表皮LC及DETC的密度及形态变化。结果:(1)密度变化:拔毛后1天LC及DETC与拔毛前无明显变化。拔毛后第2天开始二者密度较拔毛前升高(P<0.05),拔毛后第4~8天二者密度最高(P<0.01),以后逐渐下降,至拔毛后第17~20天二者密度基本恢复到拔毛前数值。(2)形态变化:拔毛前后2天内,多数LC及DETC胞体小,树突短小不明显;第4~8天,二者多数细胞体大,树突多且粗大,分枝明显;9~16天,胞体大小不一,树突变细;17~20天,胞体较小,树突短小。结论:拔毛诱导的小鼠毛发周期中毛囊间表皮LC及DETC的密度及形态变化与毛囊周期具有相关性。这种变化在皮肤免疫应答中可能起重要作用。