Distinctive dendritic cell subsets expressing factor XIIIa, CD1a, CD1b and CD1c in mycosis fungoides and psoriasis

The papillary dermis of psoriasis and mycosis fungoides (MF) lesions is characterized by prominent collections of cells with dendritic morphology. Immunophenotypically distinct populations of cutaneous dendritic cells have been identified as CD1a+, FXIIIa-Langerhans cells (LC) and CD1a-, FXIIIa+ dermal dendritic cells (DDC). In this study, antibodies against the human GDI cluster of antigens (i.e. CD1a, CD1b and CD1c) and the DDC) marker (FXIIIa) were used to further characterize the subsets of dendritic cells in normal skin as compared to neonatal foreskin, psoriasis and MF by both immunoperoxidase and double immunofluorescence techniques. Normal skin and foreskin epidermis and dermis contained few CD1b+ or CD1c+ cells along with normal numbers of CD1a+ LC and FXIIIa+ DDC. Both MF and psoriasis were characterized by CD1a+ cells in the epidermis and dermis. FXIIIa+ cells were greatly expanded in the upper dermis of MF lesions and to a lesser degree in psoriasis as has been previously described by our group. MF contained significantly increased epidermal and dermal CD1b+ (15.7/5 high power fields [HPF] and 59.7/5 HPF respectively) and CD1c+ dendritic cells (33.8/5 HPF and 95.9/5 HPF respectively), while in psoriasis these cells were not statistically different from normal skin. Double immunofluorescence studies revealed that some (<25%) FXIIIa+ cells co-expressed CD1b and CD1c in MF>psoriasis> foreskin, while FXIIIa+ DDC never co-expressed CD1a. Thus, in contrast to normal skin in which epidermal or dermal dendritic cells rarely express CD1b and CD1c antigens, these members of the CD1 family are upregulated on both LC and DDC in benign and malignant inflammatory states. Upregulation of CD1b and CD1c on MF epidermal and dermal dendritic cells, as compared to psoriasis, foreskin and normal skin, may be useful in the immunophenotypic recognition of MF, as well as in helping to understand its immunobiology.     

CD1a、CD68在继发性瘢痕疙瘩中的表达及意义

目的 探讨继发性瘢痕疙瘩皮损中表皮朗格汉斯细胞（LC）和真皮CD68阳性组织细胞的分布和密度。方法 取30例继发性瘢痕疙瘩患者的皮损、14例正常人皮肤组织切片进行CD1a和CD68免疫组化染色。以测微尺标定目镜方格计数方格内阳性细胞数,计算出单位面积内细胞的密度。组间比较采用SPSS软件进行 Student t检验。结果 在继发性瘢痕疙瘩表皮内CD1a阳性LC密度为（61 ± 49）个/mm2,正常表皮为（258 ± 61）个/mm2,两组比较,t = 9.88,P ＜ 0.01;继发性瘢痕疙瘩真皮CD1a阳性细胞密度为（40 ± 65）个/mm2。继发性瘢痕疙瘩表皮中无CD68阳性细胞,真皮内CD68阳性组织细胞密度为（287 ± 73）/mm2,正常皮肤为（290 ± 22）个/mm2,两组比较,t = 0.02,P ＞ 0.05。继发性瘢痕疙瘩真皮浅层CD68阳性组织细胞占真皮中所有细胞的62% ± 12%,而正常皮肤为70% ± 14%,两组比较,t = 2.66,P ＜ 0.05。 结论 继发性瘢痕疙瘩表皮中LC减少,无CD68阳性的细胞。真皮中LC增多;真皮浅层CD68阳性组织细胞占真皮中所有细胞的比例下降。     

Profiles of Foxp3+ regulatory T cells in eczematous dermatitis, psoriasis vulgaris and mycosis fungoides

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.     

Prurigo pigmentosa: role of ICAM-1 in the localization of the eruption

Immunohistochemical studies were carried out on the skin lesions of two cases of prurigo pigmentosa. There was a predominance of CD4+ cells in the dermal infiltrate, whereas those lymphocytes in the epidermis were mainly CD8+ cells. The majority of dermal and epidermotropic lymphocytes showed an intense expression of lymphocyte function-associated antigen 1 (LFA-1). The number of CD1+ cells was increased in the epidermis. There was intense expression of ICAM-1 by keratinocytes in the erythematous papules. Focal expression of ICAM-1 was still observed in the residual pigmented areas and could explain the recurrence of the lesions at these sites.     

Increased expression of TRAIL and its death receptors DR4 and DR5 in plaque psoriasis

TNF-related apoptosis-inducing ligand (TRAIL) is recognized as an important regulator of immune responses during infections and various autoimmune-mediated pathologies. Its role in inflammatory dermatoses is largely unknown. We aimed to investigate the expression of TRAIL and its receptors DR4 and DR5 in psoriasis vulgaris. Immunohistochemistry for TRAIL, DR4 and DR5 was performed on samples of lesional (n = 10) and non-lesional (n = 10) skin of patients with plaque psoriasis and skin of healthy volunteers (n = 10). Expression of TRAIL and its receptors was further examined by means of double immunofluorescence staining and co-localization with CD4, CD8, CD11c, CD68, CD16 and CD56 markers. Immunohistochemical staining for TRAIL was significantly enhanced in psoriatic lesional as well as non-lesional epidermis compared to the epidermis of healthy skin. Lesional epidermis also showed increased immunoreactivity for DR5. In addition, expression of TRAIL and both of its receptors was significantly increased in the dermis of lesional skin. As evidenced by double immunofluorescence, TRAIL was readily expressed by most of the examined cells of the inflammatory infiltrate in psoriatic lesions. In contrast, the expression of DR4 was found mostly among CD4+ and CD8+ cells but was only nuclear, while DR5 showed cytoplasmic staining in rare CD16+, CD56+ and CD68+ cells. According to abundant in situ presence of TRAIL and its receptors in lesional psoriatic skin, it seems that this cytokine participates in the complex interplay between keratinocytes and cells of the dermal infiltrate and thus contributes to the inflammatory cycle in psoriasis vulgaris.     

银屑病皮损CD8αα+ T细胞表型鉴定

目的 探究银屑病皮损局部浸润的CD8+ T细胞表型及其在银屑病发病中的作用。方法 收集2017年1 - 12月第四军医大学西京皮肤医院明确诊断的8例进行期斑块状银屑病患者皮损,男女各4例,年龄24 ~ 50岁。8例健康对照皮肤来源于整形外科手术剩余皮肤,男女各4例,年龄23 ~ 46岁。采用免疫荧光技术检测皮损CD8+ T细胞的分布及亚群比例,鉴定其免疫学表型及炎症因子白细胞介素（IL）17A的表达。结果 8例银屑病皮损真、表皮均可见CD8+ T细胞浸润,其中CD8αα+ T细胞表型占88.48% ± 7.39%,8例健康人皮肤局部仅有个别CD8+ T细胞浸润,其中CD8αα+ T细胞表型占14.43% ± 13.14%,两组比较,t = 11.5,P < 0.01。银屑病皮损表皮CD8αα+ T细胞表达组织局部定植标志CD103,真皮CD8αα+ T细胞不表达CD103。银屑病皮损CD8αα+ T细胞表达CD45RA-CCR7-效应记忆性T细胞表型,不表达CD8+ 调节性T细胞标志Foxp3、CD25和CD122。银屑病皮损CD8αα+ T细胞中分泌IL?17A的细胞比例为24.85% ± 4.25%,对照组CD8αα+ T细胞不分泌IL?17A,两组差异有统计学意义（t = 5.853,P < 0.01）。结论 银屑病皮损浸润的CD8αα+ T细胞是效应记忆性T细胞,可能通过分泌IL?17A参与银屑病的发生发展。     

他克莫司软膏对银屑病患者皮损T细胞的影响

目的观察他克莫司软膏对银屑病皮损处T细胞的影响。方法采用免疫组化法检测10例寻常性银屑病(斑块型)患者应用0.1%他克莫司软膏治疗前、后的皮损组织及10例正常健康人的皮肤组织中CD3,CD4及CD8T细胞的表达。结果 0.1%他克莫司软膏治疗后,银屑病皮损的表皮层CD3,CD4及CD8T细胞降低不明显,真皮层CD3,CD4及CD8T细胞的表达明显减少。结论他克莫司软膏对银屑病皮损处CD3+、CD4+和CD8+T细胞有显著的抑制作用。     

The use of immunohistologic analysis in differentiating cutaneous T-cell lymphoma from psoriasis and dermatitis

BACKGROUND AND DESIGN.--Many investigators have applied immunohistologic analysis to skin biopsy specimens to distinguish cutaneous T-cell lymphoma (CTCL) from benign inflammatory diseases, such as psoriasis and dermatitis, which can clinically mimic early-stage CTCL. We studied the number and distribution of epidermal cells labeled with various monoclonal antibodies in normal skin and in psoriatic, dermatitic, and CTCL lesions by the immunoperoxidase technique. RESULTS.--Extensive staining of keratinocytes (KCs) with HLA-DR was seen in 27 of 41 patients with CTCL, but in only one of 14 patients with psoriasis and zero of 10 patients with dermatitis. CD2+ and CD3+ cells were present in the middle and upper epidermis of CTCL lesions in much greater numbers than in normal, dermatitic, and psoriatic skin. The percent epidermal area covered by CD1+ cells in psoriatic lesions (1.13%) and dermatitic lesions (1.65%) was significantly lower than that found in CTCL lesions (3.60%). CONCLUSION.--Epidermal immunohistologic patterns using anti-CD1, anti-CD2, anti-CD3, and anti-HLA-DR antibodies have the potential to distinguish CTCL from psoriasis and dermatitis in clinically ambiguous cases.     

Proliferative activity of CD8(+) T cells as an important clue to analyze T cell-mediated inflammatory dermatoses

Abstract To elucidate the pathogenesis of T cell-mediated inflammatory skin diseases, we examined the exact sites where CD8(+) T cells proliferate, correlating them with the localization of antigen-presenting dendritic cells. We performed CD8/Ki-67 double immunohistochemical staining and single staining for CD1a, CD68, and factor XIIIa on sections of paraffin-embedded tissue samples of inflammatory dermatoses in which T lymphocytes are thought to play a crucial role. The dermatoses were lichen planus (12 samples), acute graft-versus host disease (GVHD) (12 samples), chronic GVHD (10 samples), spongiotic dermatitis (8 samples) and psoriasis (7 samples). Labelling for Ki-67 among CD8(+) T cells was predominantly observed in the subepidermal lymphoid infiltrate, and was scanty in the epidermis. This suggested that proliferation of CD8(+) T cells occurred preferentially in the dermis. The labelling index for Ki-67 among dermal and epidermal CD8(+) cells was quite different among the different diseases studied (P < 0.05). They were rich in the subepidermal portion of the dermis of spongiotic dermatitis, acute GVHD and chronic GVHD, but rare in the dermis of psoriasis and lichen planus. A moderate infiltrate was also observed in lesional epidermis of spongiotic dermatitis, acute GVHD and chronic GVHD, whereas they was almost none in the epidermis of psoriasis and lichen planus. CD1a(+) dermal dendritic cells were densely distributed within the lymphoid infiltrate in the affected dermis of spongiotic dermatitis, psoriasis and lichen planus, whereas they were minimal in GVHD. These dermal dendritic cells are candidates as stimulators on T cells in the dermis. In conclusion, the proliferative status of T cells could be an important clue in the elucidation of the pathophysiology of T cell-mediated inflammatory dermatoses. Received: 13 December 2000 / Revised: 24 April 2001 / Accepted: 11 July 2001     

Homing receptor and chemokine receptor on intraepidermal T cells in psoriasis vulgaris

Intraepidermal T lymphocytes found in psoriatic skin lesions are involved in the development and maintenance of lesional pathology. It has become clear that differential expression of homing and chemokine receptors determines the specific migration of T cells to distinct tissues and microenvironments, including psoriasis lesions. The aim of the present study was to clarify expression of homing (CLA, VLA-4, and LFA-1) and chemokine (CCR4, CCR6, CCR7, and CXCR3) receptors on intraepidermal T cells in psoriatic lesions using flow cytometry. The vast majority of intraepidermal T cells in psoriatic lesions expressed CLA and LFA-1, whereas 58% of CD4+ and 85% of CD8+ T cells expressed VLA-4. The majority of CD4+ T cells and about half of the CD8+ T cells expressed CCR4 and CCR6, whereas less than one-third of CD4+ and CD8+ T cells expressed CXCR3 or CCR7. In patients with psoriasis the percentages of T cells expressing CLA, CCR4, and CCR6 were much higher in the epidermis of psoriatic plaques than in the peripheral blood. Thus, CLA, CCR4, and CCR6 may play a more important role in the migration of T cells to psoriatic epidermis.     

Toll样受体2和4在银屑病皮损中的表达

目的研究Toll样受体（TLR）2和4在银屑病皮损中的表达，探讨其与银屑病发病的关系。方法选用16例滴状银屑病、13例斑块状银屑病患者及10例正常人皮肤的石蜡切片．用免疫组化的方法研究TLR2和TLR4的表达。结果10例正常人皮肤的基底层均有较弱的TLR2表达而无TLR4表达．真皮血管内皮细胞未见TLR2及TLR4表达。所有16例滴状银屑病、13例斑块状银屑病皮损的基底细胞层均可见明显的TLR2表达，棘层也有弱表达；TLR4则呈现表皮全层的弥漫性强表达。银屑病真皮浅层血管内皮细胞可见明显的TLR2及TLR4表达。结论TLR2、TLR4在银屑病皮损均有表达，TLR4的表达更高：提示感染相关免疫与银屑病发病关系密切。     

Epidermal CD8+ T cells reactive with group A streptococcal antigens in chronic plaque psoriasis

Chronic plaque psoriasis is a T cell mediated disease associated with group A streptococci (GAS). We have previously shown the presence of a psoriasis-specific dermal Th1 subset that recognizes GAS antigens. To assess whether GAS-reactive T cells are also present in lesional epidermis, fresh cell suspensions or T cell lines isolated from lesional epidermis of 33 psoriasis patients were stained for intracellular interferon-gamma after stimulation with GAS antigens. The patients were typed by PCR for HLA-DR7 and HLA-Cw6 expression. A subset of GAS-reactive CD8+ T cells (2.4% +/- 2.4) was found in 14/21 (67%) fresh cell suspensions. A smaller subset of GAS-reactive CD4+ T cells (0.9% +/- 0.9) was found in 13/21 (62%) fresh cell suspensions, which was expanded in the T cell lines. There was a significant inverse correlation between the proportions of GAS-reactive CD4+ and CD8+ T cells in the fresh suspensions (r = -0.48, P = 0.0277). The presence of GAS-reactive CD4+ or CD8+ T cells did not correlate with HLA-DR7 or HLA-Cw6 expression, respectively. This study has demonstrated GAS-reactive CD8+, and to a lesser extent CD4+, T cell subsets in psoriatic epidermis and provides further evidence that GAS antigens may play a role in the pathogenesis of chronic plaque psoriasis.     

Hyaluronan and CD44 in psoriatic skin. Intense staining for hyaluronan on dermal capillary loops and reduced expression of CD44 and hyaluronan in keratinocyte-leukocyte interfaces

The distributions of hyaluronan (HA) and its presumptive receptor, CD44, were studied in skin samples from 13 psoriasis vulgaris patients, using an HA-specific probe (HABC), and monoclonal antibodies, respectively. The general distribution of HA and CD44 in psoriatic lesional epidermis resembled that in normal epidermis. However, areas of epidermis invaded by leukocytes showed a local depletion of HA and CD44, particularly at the contact areas of keratinocytes to lymphocytes and neutrophils. Removal by cellular uptake or extracellular degradation of CD44 and HA may be required for tight adherence between a keratinocyte and a leukocyte. On the dermal side, the tips of the prolonged dermal papillae in psoriatic lesions were intensively stained with HABC. The dilated capillaries and the space below the tip basal lamina, in particular, were heavily covered with HA. Occasionally, a similar intense staining was seen around an enlarged capillary in uninvolved psoriatic skin. CD44-positive leukocytes were found around the affected capillaries. The accumulation of HA in the dermal papillae may support the growth of psoriatic lesions, since HA stimulates the growth of capillaries as well as attracting inflammatory cells.     

银屑病患者皮肤中T细胞与黑素细胞的检测及临床意义

目的 研究银屑病患者皮肤中CD4+和CD8+ T细胞与黑素细胞的关系和临床意义。 方法 取29例进行期银屑病患者皮损和非皮损、5例消退期患者皮损和非皮损及6例健康人皮肤。免疫组化检测CD4+ T细胞和CD8+ T细胞的数量和分布,并对比基底层黑素细胞和色素颗粒情况。采用SPSS18.0软件进行统计分析,多组间比较采用单因素方差分析（ANOVA）,两组间比较采用最小显著差异法（LSD）,相关性分析采用Pearson检验。 结果 银屑病患者皮损中每个高倍（× 200）视野CD4+ T细胞平均数（表皮5.29 ± 4.66,真皮77.50 ± 43.66）明显高于非皮损（表皮为0,真皮9.67 ± 7.73）,皮损与非皮损比较,均P ＜ 0.05;而CD8+ T细胞的数量（表皮7.83 ± 6.27,真皮46.08 ± 34.26）亦明显高于非皮损（表皮0.71 ± 1.20,真皮5.54 ± 4.43）,皮损与非皮损比较,均P ＜ 0.05。与健康对照皮肤相比,银屑病患者皮损中CD4+ T细胞和CD8+ T细胞均明显增多,差异有统计学意义（均P ＜ 0.05）。银屑病皮损处基底层黑素细胞数量（103.45 ± 16.96）明显高于非皮损（43.62 ± 14.20,P ＜ 0.05）及健康人皮肤（P ＜ 0.05）,但色素颗粒阳性细胞比例（7.45% ± 3.86%）明显低于非皮损（43.10% ± 14.91%,P ＜ 0.05）及健康人皮肤（P ＜ 0.05）。非皮损处CD8+ T细胞、CD4+ T细胞、黑素细胞数量及色素颗粒阳性细胞比例与健康人比较差异均无统计学意义。消退期皮损黑素细胞数量高于消退后白斑（P ＜ 0.05）,色素颗粒阳性细胞比例略低于消退后白斑,但差异无统计学意义;与健康人比较,消退期皮损黑素细胞数量高,而色素颗粒阳性细胞比例低,均有统计学差异（均P ＜ 0.05）,消退后白斑的黑素细胞数量与健康人比较差异无统计学意义,而色素颗粒阳性细胞比例降低（P ＜ 0.05）。进行期患者皮损中CD4+、CD8+ T细胞数与黑素细胞数及色素颗粒阳性细胞比例均无相关性（均P > 0.05）,而非皮损中CD4+、CD8+ T细胞数与黑素细胞数呈正相关（r值分别为0.46和0.56,均P ＜ 0.05）,但与色素颗粒阳性细胞比例无明显相关性（P > 0.05）。 结论 在银屑病进行期皮损中,CD4+ T细胞和CD8+ T细胞明显增多,基底层黑素细胞数量增加,但色素颗粒明显减少;皮损消退后,黑素细胞数量及色素颗粒逐渐接近健康人水平。     

Perforin expression is upregulated in the epidermis of psoriatic lesions

BACKGROUND: There are currently very few data regarding the role of cell-mediated cytotoxicity in psoriasis. Both cytotoxic T lymphocytes and natural killer (NK) cells mediate cytotoxicity reactions, mainly by two distinct pathways, the perforin/granzyme and the Fas/Fas ligand pathway. OBJECTIVES: To study the expression and distribution of perforin, T- and NK-cell subsets in psoriatic lesional and nonlesional skin. METHODS: Skin biopsy specimens from both lesional and nonlesional skin of 11 patients with chronic plaque psoriasis and eight healthy controls were analysed by immunohistochemistry. RESULTS: We found a significant increase in CD4+ and CD8+ cells in psoriatic lesions compared with nonlesional and healthy skin. The expression of CD16+ NK cells was significantly lower in lesions compared with healthy skin. Perforin expression was significantly enhanced in the epidermis of psoriatic lesions. CONCLUSIONS: Perforin expression is upregulated in the epidermis of psoriatic lesions, suggesting a potential role for perforin in the creation of the psoriatic plaque.     

CD103+T细胞在银屑病皮损中的表达

目的：明确银屑病患者皮肤CD103+T细胞的表达及其与银屑病严重程度的关系。方法：免疫组化检测29例银屑病患者皮损和非皮损皮肤及6名健康对照皮肤中表皮及真皮CD103+T细胞的表达。计算银屑病患者PASI值。结果：CD103+T细胞主要在真皮表达。银屑病患者皮损和非皮损真皮中每个高倍视野CD103+T细胞百分率分别为（26.06%±11.72）%和（12.82±4.5）%（P<0.05）;健康人对照皮肤真皮内CD103+T细胞百分率为（7.47±1.3）%,明显低于银屑病非皮损区（P<0.05）。银屑病患者皮损中,CD103+T的表达与PASI值正相关（P<0.05）。 结论：真皮中CD103+T细胞可能与银屑病的发病及严重程度有关。     

寻常型银屑病皮肤中皮肤归巢T细胞免疫组化研究

目的 探讨皮肤归巢T细胞在寻常型银屑病(PV)发病中的作用。方法 采用间接免疫荧光双标法研究正常人皮肤和PV患者皮肤中浸润的皮肤归巢T细胞分类及其变化。结果 ①正常人皮肤及PV皮损中浸润的T细胞绝大多数表达皮肤淋巴细胞相关抗原(CLA),CLA⁺细胞高度表达CD45RO,只有个别为CD45RO阴性。②进行期皮损CD4⁺CLA⁺及CD8⁺CLA⁺T细胞数高于静止期皮损(P<0.05),静止期皮损CD4⁺CLA⁺细胞数高于消退期皮损(P<0.05),消退期皮损CD8+CLA+细胞数高于PV外观正常皮肤(P<0.05),进行期皮损周边外观正常皮肤CD4⁺CLA⁺及CD8⁺CLA⁺细胞数高于静止期皮损周边外观正常皮肤(P<0.05).③部分病例皮损的表皮中见大量CLA⁺树突状细胞,正常人皮肤未见此细胞。结论 正常人皮肤及PV皮损中T细胞绝大多数为皮肤归巢T细胞;进行期及静止期PV皮损中浸润的细胞主要为CD3⁺、CD4⁺、CD45RO⁺、CLA⁺T细胞,CD3⁺、CD4⁺、CD45RO⁺、CLA⁺T细胞可能在PV发病中起重要作用。     

Reticulate hyperpigmentation distributed in a zosteriform fashion: a new clinical type of hyperpigmentation

Sequential skin biopsies from six patients with severe psoriasis were studied during treatment with cyclosporin. Four of the patients cleared completely and the remaining two showed a marked improvement. A subset of dendritic cells, HLA-DR+ but lacking the T6 antigen characteristically expressed by Langerhans cells (DR+ 6-), was observed in lesional epidermis. They disappeared during treatment, before clinical improvement was apparent and at a rate which correlated with clearance of psoriasis. These cells were not found in normal or uninvolved psoriatic epidermis and their number in lesional skin appeared to be related to the clinical severity of the disease. Total numbers of CD4 and CD8, and HLA-DR+ CD8 T cells were substantially reduced in both epidermis and dermis prior to clinical improvement. In contrast, there was generally no decrease in the number of HLA-DR+ CD4 T cells in the epidermis during resolution, whereas these cells were reduced by an average of 68% in the dermis. The beneficial effects of cyclosporin in psoriasis further support the hypothesis that T cells play a central role in the pathogenesis of psoriasis. The cellular changes observed in the skin during cyclosporin treatment may help to elucidate the effects of this drug on immunoregulatory mechanisms in man.     

Immunohistochemical Studies of Infiltrating Cells in Early and Chronic Lesions of Psoriasis

The expression of surface antigens on infiltrating cells, epidermal keratinocytes, and dendritic cells in biopsy specimens from 31 patients with psoriasis was examined immunohistochemically. The specimens were divided into early-phase and chronic-phase groups and then examined in a double blind manner. Among the infiltrating cells in the epidermis, CD4-positive cells were dominant in the early phase; CD8-positive cells were dominant in the chronic phase, resulting in a markedly decreased CD4/CD8 ratio in the latter. On the other hand, among the infiltrating cells in the dermal papillae, CD4-positive cells were dominant in both the early and chronic phases; both CD4-positive and CD8-positive cells were more dominant in the chronic phase than in the early one. However, the CD4/CD8 ratios were decreased in both the dermal papillae and the epidermis in the chronic phase. CD1-positive dendritic cells (probably Langerhans cells) were more numerous in the chronic phase than in the early phase. There were no significant differences between the early and chronic phases with regard to the expression of HLA-DR and HLA-DQ antigens on the infiltrating cells. However, the HLA-DR antigens and ICAM-1 (intercellular adhesion molecule-1) were more strongly expressed on epidermal keratinocytes in the chronic phase than in the early phase. LFA-1α (lymphocyte function-associated antigen-1α)-positive cells were also significantly more numerous in the chronic phase than in the early one, consistent with the expression of HLA-DR antigens and ICAM-1 on keratinocytes mentioned above. On the other hand, VLA-4 (integrin α₄β₁) positive cells were expressed more abundantly in the epidermis in the early phase than in the chronic phase. These results suggest, first, that the chronic phase of psoriasis is as immunologically active as or more active than the early phase. Second, CD4-positive T cells are more important than CD8-positive T cells in the early phase of psoriasis; CD8-positive rather than CD4-positive T cells are more important in the chronic phase. Third, the LFA-1/ICAM-1 pathway may play an important role with regard to cell adhesion of the infiltrating cells in the psoriatic lesions in disease exacerbation or prolongation, whereas the VLA-4/VCAM-1 (vascular cell adhesion molecule-1) pathway may be more important in disease onset.     

Immunohistochemical differentiation between inflammatory linear verrucous epidermal nevus (ILVEN) and psoriasis

Inflammatory linear verrucous epidermal nevus (ILVEN) is a rare skin disorder with a clinical and histological resemblance to psoriasis. In the past clinical and histological criteria have been defined. However, there remains a discussion as to whether ILVEN is a disease entity distinct from linear psoriasis. Our objective was to compare by quantitative immunohistochemistry the subsets of T-lymphocytes and markers for epidermal growth and keratinisation in biopsies taken from skin lesions of 4 patients with psoriasis and 3 patients with ILVEN: 1. patients with psoriasis (case 1-4) 2. patient with ILVEN cum psoriasis (case 5) 3. patients with ILVEN sine psoriasis (case 6 and 7). Our aim was to delineate ILVEN from psoriasis. Four patients with active psoriasis and three patients with signs and symptoms of ILVEN are described in this case report. Two patients of the ILVEN group had only linear verrucous lesions (ILVEN sine psoriasis), and one patient had linear lesions combined with widespread psoriasis outside the linear verrucous lesion (ILVEN cum psoriasis). The following markers were investigated in skin biopsies taken from the aforementioned patients by quantitative immunohistochemistry: CD2, CD4, CD8, CD25, CD161, CD94, CD45RO, CD45RA, HLA-DR, Keratin-10, Ki-67. In patients with ILVEN (cum and sine psoriasis) the number of Ki-67 positive nuclei, tended to be lower, the number of keratin-10 positive cells and HLA-DR expression higher as compared to psoriasis. In ILVEN sine psoriasis all T-cell subsets and cells expressing NK receptors were reduced as compared to psoriasis, except for CD45RA+ cells, whereas in the patient with ILVEN cum psoriasis the number of these T cell subsets had an intermediary position. In particular the density of CD8+, CD45RO+ and CD2+, CD94 and CD161 showed a marked difference between ILVEN sine psoriasis and psoriasis. In addition to the increased keratin 10 expression in ILVEN sine psoriasis, T cells relevant in the pathogenesis of psoriasis are markedly reduced in ILVEN sine psoriasis as compared to psoriasis. T-cell subsets in ILVEN cum psoriasis had an intermediary position.