Expression of serotonin receptors in allergic contact eczematous human skin

The expression of the serotonin (5-HT) receptors 5-HT1AR, 5-HT2AR and 5-HT3R was investigated in allergic contact eczematous human skin by an indirect fluorescence method. 5-HT1AR expression was found in basal epidermal NK1-beteb-positive cells, which were more elongated and showed longer dendritic processes in contact eczematous skin than in control skin. Immunoreactivity for 5-HT1AR was also found in the upper part of the epidermis, with no difference between eczematous and control skin. 5-HT1AR expression was also found in 33.3+/-6.5% and 63.7+/-11.3% of papillary dermal mononuclear cells in inflamed skin and control skin, respectively ( P<0.001), as well as in vessel walls. Some of these mononuclear cells were tryptase-positive, and found in both eczematous and control skin. 5-HT2AR-positive cells were found in the upper part of the epidermis in eczematous skin, but were more evenly distributed in the epidermis of control skin. In addition, inflammatory dermal mononuclear cells and vessel walls showed immunoreactivity for this receptor. 5-HT3R expression was found in the basal epidermal layer of eczematous and control skin. These findings indicate a plasticity in the effects of serotonin, especially regarding 5-HT1AR, in allergic contact eczematous skin.     

The serotonin transporter protein is expressed in psoriasis,where it may play a role in regulating apoptosis

Since the symptoms of psoriasis may be changed by treatment with selective serotonin reuptake inhibitors (SSRIs), the expression of serotonin (5-HT) and its transporter protein (SERT) in the skin of patients with psoriasis were examined employing a biotinylated-streptavidine procedure. In biopsies of such skin staining for 5-HT was limited to platelets; the expression of SERT in the keratinocytes of involved regions was redistributed; the numbers of SERT-positive dendritic or round mononuclear cells in the epidermis of involved psoriatic skin were higher than in normal healthy control skin; and the dermis of the involved skin contained higher numbers of round inflammatory cells immunostained for SERT than either non-involved psoriatic skin or normal skin. Double-immunostaining indicated that the skin cells expressing SERT also expressed CD1a, CD3 or tryptase. In addition, SERT immunostaining was co localized with caspase-3, a key regulator of apoptosis, but not with TUNEL staining. The present findings indicate that SERT might play a role in regulating apoptosis in inflammatory cells associated with psoriasis, in which case this protein might constitute a valuable therapeutic target.     

The expression of serotonin transporter protein correlates with the severity of psoriasis and chronic stress

Psoriasis may be worsened by stress and mood disorders. There is an increased expression of the serotonin transporter protein (SERT) in involved psoriatic skin as compared to non-involved psoriatic skin and normal skin. The aim of this study was to investigate if the increased expression of SERT in psoriasis correlates with the severity of disease, chronic stress, and depression. Biopsies from involved and non-involved skin from the back of 20 patients with chronic plaque psoriasis were immunohistochemically analysed, using a monoclonal antibody to SERT. The severity of psoriasis was assessed for each patient using the Psoriasis area and severity index (PASI). Levels of depression and chronic stress were measured using Beck’s Depression Inventory (BDI) and the salivary cortisol test, respectively. A positive correlation (r = 0.53; p < 0.05) between PASI and the numbers of SERT-positive dendritic cells in the epidermis of involved psoriatic skin was determined. We also observed a negative correlation (r = ?0.46; p < 0.05) between salivary cortisol ratio levels and the numbers of SERT-positive cells in the epidermis of involved psoriatic skin, indicating a correlation between SERT expression and chronic stress. The serotonergic system may be involved in the chronic inflammation evident in psoriatic skin. Through modulating the levels of SERT, there might be a therapeutic possibility for reducing chronic inflammation in psoriasis.     

Study of substance P and its receptor neurokinin-1 in psoriasis and their relation to chronic stress and pruritus

Substance P and its receptor(R) neurokinin (NK)-1 may have a role in the pathogenesis of psoriasis. Stress has been reported to play a role in the onset and exacerbation of psoriasis, which might include the substance P-NK-1 receptor(R) pathway. A feature of psoriasis, that has been correlated to the severity of stress and secretion of substance P, is pruritus. The objective of this study was to investigate the expression of substance P and the NK-1R in involved and noninvolved psoriatic skin, using a biotinylated streptavidin technique. Moreover, a possible correlation between the patient′s level of chronic stress, measured by salivary cortisol samples, degree of lesional pruritus, measured by means of a visual analogue scale, and the expression of substance P- and the NK-1R, was investigated. There was a low number of substance P positive nerve fibres in noninvolved and involved skin, the major immunoreactivity for substance P being found in inflammatory cells. The number of substance P- and NK-1R positive inflammatory cells was increased in involved compared to noninvolved psoriatic skin. The substance P positive cells were mostly lymphocytes, while most of the NK-1R positive cells were mast cells. NK-1R immunoreactivity was also seen as a reticular pattern in the upper part of the epidermis of involved skin in the majority of the patients. Low cortisol ratios in the patients, being an indicator of chronic stress, were correlated to an increased number of substance P- and NK-1R positive inflammatory cells in noninvolved psoriatic skin, and higher cortisol ratios to the presence of keratinocyte NK-1R immunoreactivity in involved skin. The degree of pruritus could not be correlated to the number of substance P positive fibers nor cells. Nonneuronal substance P and its receptor NK-1 might have a role in psoriasis, also during chronic stress.     

Characterization of activity of alkaline phosphatase (AAP) in capillary endothelium of normal and psoriatic skin

Summary The activity of alkaline phosphatase (AAP) in papillary capillaries of normal and psoriatic skin was characterized by enzyme inhibition studies. Quantitatively, there were pronounced differences between normal and psoriatic skin, i.e., increase of AAP, as determined by a grading system, and assimilation of the strength of AAP in venous and arterial side of the capillary loop in psoriasis.Qualitatively, the inhibition studies with different acting inhibitors revealed no difference between AAP in normal and psoriatic skin or between initial, fully developed and healed psoriatic lesions as well as noninvolved skin of psoriatics. Thus, the physiologic AAP seems to be stimulated in psoriasis.Generally, AAP of dermal capillaries is highly sensitive to cysteine inhibition.Dedicated to Professor Dr. W. Schneider on his 70th anniversary     

Silencing of homeobox A5 gene in the stratum corneum of psoriasis

Analysis of psoriatic parakeratotic cells is helpful for understanding the pathogenesis of psoriasis. Methylation analysis can be performed on psoriatic scales, but it is unclear whether genes can be silenced by DNA methylation in psoriatic stratum corneum. The present study was conducted to detect genes silenced in psoriatic stratum corneum. Methylation array analysis with 485 577 probes, quantitative real‐time methylation‐specific PCR (RT‐MSP) and bisulphite sequencing were performed for 30 psoriatic scale samples, 6 fully developed psoriatic skin samples and 12 normal skin samples. Immunohistochemical staining of HOXA5 was performed for 29 psoriatic epidermal samples and 13 normal epidermal samples. The genome‐wide methylation array detected two CpG sites within CpG islands (CGIs) located in promoter regions of HOXA5 and LIAS that had methylation levels of >0.6 in at least one of the three psoriatic scale samples and of <0.2 in all three normal skin tissue samples (methylation rate range, 0.0‐1.0). RT‐MSP for HOXA5CGI, in which the primers were successfully developed, revealed that the average methylation level of 27 psoriasis scales (60.2%) is significantly higher than that of 9 normal skin samples (34.6%) (P=.013). Immunohistochemical staining revealed that HOXA5 protein was not expressed in the stratum corneum of fully developed psoriatic epidermis, but the protein was expressed in the stratum corneum of incompletely developed epidermis and normal epidermis. In conclusion, HOXA5 can be silenced in the stratum corneum of psoriasis. The silenced gene was identified by non‐invasive methylation analysis of psoriatic scales.     

Life events involvement in psoriasis onset/recurrence

Background The purpose of the study was to evaluate the possible role of stress before the onset/extension/recurrence of psoriasis. Patients and method One hundred and sixty‐nine outpatients with psoriasis and 169 age and gender matched controls were enrolled. The design was a case‐control study (controls had skin diseases with low psychosomatic component). Stressful life events were evaluated using Holmes and Rahe’s Social Readjustment Rating Scale. Results In the psoriatic group, there was a female predominance (66%) and a median age 47.55 years (SD = 20.32). In all, 10.65% of patients had family history of psoriasis. More than 54% of cases experienced at least one stressful event (47.36% for onset, 63.51% for recurrence/extension), compared with 19.52% of controls (χ² = 42.71, P < 0.0001). The odds ratio was 4.92. There was a significant difference in the mean number of stressful events between patients and controls (P < 0.0001). Women with psoriasis vulgaris and men with guttate psoriasis seemed to be more sensitive to stressful events. We divided the events described by Holmes and Rahe into three categories: family, personal, and job/financial problems. Family matters were mentioned by 42.7% of psoriatic patients, statistically significant compared with controls (P < 0.0001). In 35% of psoriatic cases, “the stressful event” was represented by the illness/death of someone dear. Both “personal” (25.6%; P = 0.02) and “job/financial problems” (31.6%; P < 0.0001) were significantly different compared with controls. Conclusions Stressful events could be highly related to psoriasis (especially in recurrences/extensions). Problems related to family are the most often involved with counseling being suggested.     

Serotonergic mechanisms in human allergic contact dermatitis

Expression of serotonin (5-hydroxytryptamine; 5-HT), 5-HT receptors 1A (5-HT1AR) and 2A, and serotonin transporter protein (SERT) was studied in positive epicutaneous reactions to nickel sulphate in nickel-allergic patients, at 72 h post-challenge with the antigen. In addition, the effects of 5-HT2AR agonist 2,5-dimethoxy-4-iodoamphetamine (DOI), and the selective serotonin reuptake inhibitors (SSRIs) citalopram and fluoxetine, were tested on nickel-stimulated peripheral blood mononuclear cells from nickel-allergic patients, regarding their proliferation and interleukin (IL)-2 production, as well as the effect of these SSRIs on a murine Langerhans' cell-like line (XS52), regarding its IL-1beta production. Serotonin-positive platelets were increased in the inflamed skin compared with control skin. A decrease (p <0.01) in 5-HT1AR-positive mononuclear cells was evident in the eczematous skin compared with control skin, whereas 5-HT2AR- and SERT-positive cells were increased (p <0.001 for both) in the eczematous skin. Treatment of nickel-stimulated peripheral blood mononuclear cells with 5x10(-5) mol/l of DOI inhibited (p <0.01) the proliferation of nickel-stimulated peripheral blood mononuclear cells, while no effect was found regarding IL-2 production. Citalopram at 10(-6) mol/l tended to inhibit the production of IL-1beta by the XS52 cell line. These results indicate the implication of the serotonergic system in the contact allergic reaction.     

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.     

Altered [125I]epidermal growth factor binding and receptor distribution in psoriasis

Stimulation of growth and differentiation of human epidermis by epidermal growth factor (EGF) is mediated by its binding to specific receptors. Whether EGF receptors primarily mediate cell division or differentiation in hyperproliferative disease such as psoriasis vulgaris is unclear. To study the pathogenesis of psoriasis, 4-mm2 punch biopsy specimens of normal, uninvolved, and involved psoriatic skin were assayed for EGF receptors by autoradiographic, immunohistochemical, and biochemical methods. Using autoradiographic and immunohistochemical methods, basal keratinocytes were found to contain the greatest number of EGF binding sites and immunoreactive receptors as compared to the upper layers of the epidermis in both normal epidermis and psoriatic skin. No EGF receptor differences between normal and psoriatic epidermis were observed in this layer. In the upper layers of the epidermis, a 2-fold increase in EGF binding capacity was observed in psoriatic skin as compared with normal thin or thick skin. Biochemical methods indicated that [125I]EGF binding was increased in psoriatic epidermis as compared with similar thickness normal epidermis when measured on a protein basis. Epidermal growth factor was shown to increase phosphorylation of the EGF receptor in skin. EGF receptors retained in the nonmitotic stratum spinosum and parakeratotic stratum corneum may reflect the incomplete, abnormal differentiation that occurs in active psoriatic lesions. Alternatively, retained EGF receptors may play a direct role in inhibiting cellular differentiation in the suprabasal layers.     

GABA and GABAA receptor expression on immune cells in psoriasis: a pathophysiological role

Psoriasis is a chronic inflammatory disease in which pruritus is a common symptom. Pruritus may be associated with the gamma-aminobutyric acid (GABA) system. The distribution of GABA and its GABA_A receptor (R) was studied in involved and non-involved psoriatic skin, as well as normal healthy control skin, using an immunohistochemistry technique. Pruritus was determined using a visual analog scale. Inflammatory cells immunoreactive for the GABA ligand and the GABA_A R were increased (P < 0.01, respectively) in the involved skin. Cells stained for GABA ligand were mostly macrophages with some lymphocytes, while cells stained for GABA_A R were macrophages, neutrophils or lymphocytes. There was a positive correlation when comparing GABA ligand (P = 0.05) and GABA_A R (P < 0.05) expressing inflammatory cells, with pruritus. The GABA ligand and its GABA_A R may play a role for the pathogenesis of psoriasis as well as for pruritus in this disease.     

Risk factors associated with having psoriatic arthritis in patients with cutaneous psoriasis

The aim of this study was to determine if the following characteristics were associated with the presence of psoriatic arthritis in a sample of psoriasis patients: race, family history of psoriasis and psoriatic arthritis, age of onset of psoriasis, smoking, alcohol consumption and the maximum body surface area (BSA) affected by psoriasis. This was a case–control study involving 400 psoriasis patients who attended the Psoriasis and Photo‐medicine clinic in the National Skin Center of Singapore over a 1‐year period. Cases were psoriasis patients with psoriatic arthritis while controls were psoriasis patients without psoriatic arthritis. The diagnosis of psoriatic arthritis was made by rheumatologists and participants completed a self‐administered standardized questionnaire. The maximum BSA involved was determined from the case notes. Psoriatic arthritis was not significantly associated with sex, race, age of onset of psoriasis, a family history of psoriasis, smoking and alcohol consumption but was significantly associated with a family history of psoriatic arthritis (P < 0.001) and the maximum body surface involved (P = 0.05). Using multivariate analysis to control for variables, the presence of psoriatic arthritis was significantly associated with a family history of psoriatic arthritis (odds ratio [OR] = 20.5; 95% confidence interval [CI] = 2.49–169.10) and the maximum BSA involved (OR = 2.52; 95% CI = 1.33–4.75). Indian psoriatic patients were more likely to have psoriatic arthritis compared to the other races. A family history of psoriatic arthritis and a greater maximum body surface involved may be associated with having psoriatic arthritis in this study population of psoriasis patients.     

Effect of chronic mild stress on serotonergic markers in the skin and brain of the NC/Nga atopic-like mouse strain

Atopic eczema is often worsened by stress. While acute stress is associated with increased turnover of serotonin (5-hydroxytryptamine; 5-HT), chronic stress causes a decrease. In chronic stress, there is a decrease of the 5-HT1A receptor (R)- and an increase in the 5-HT2AR-responsiveness to 5-HT. In the present study, the impact of chronic mild stress on the expression of 5-HT1A and 5-HT2A receptors and serotonin transporter protein (SERT) was investigated in eczematous skin and brain of atopic-like NC/Nga mice. Twenty-four NC/Nga mice were subjected to chronic mild stress for 12 weeks, and eczema was induced by applying a mite antigen (Dermatophagoides pteronyssinus) on the ears for the last 4 weeks. The mice were divided into three groups, eight per group, stressed eczematous (SE), non-stressed eczematous (NSE) and stressed control (SC). The biopsies were analysed by immunohistochemistry, using a streptavidin–biotin technique. There was an increased number of 5-HT containing dermal mast cell-like mononuclear cells in the skin of mice with eczema (SE and NSE, respectively) compared with the SC, and a tendency to more 5-HT-positive cells in the SE compared with the NSE group. Increased 5-HT1AR immunoreactivity (IR) in the skin and hippocampus of the eczematous groups compared to the control group was seen, but no difference between the SE and NSE groups. The epidermal immunoreactivity for 5-HT2AR was highest in the SE and NSE compared to the SC group, and was also higher in the SE compared to NSE. 5-HT2AR expression was also seen on nerve bundles, the number and intensity of such bundles being decreased in the SE compared to the NSE group. In the CA1 area of the hippocampus, there was an increase in the quantity of cells immunoreactive for 5-HT2AR in the SE versus the NSE group and also in the SE versus the SC group. SERT-IR was found also on nerve bundles with a decreased number in the SE compared to the NSE and SC group. There is a modulation of the expression of serotonergic markers in the eczematous skin and brain of the atopic-like mouse during chronic mild stress.     

bFGF及其受体FGFR2在银屑病皮损中的检测

目的：探讨碱性成纤维细胞生长因子（bFGF）及其受体FGFR2蛋白在银屑病皮损中的表达状态。方法：采用组织切片免疫组化技术对22例银屑病皮损和19例正常人皮肤的bFGF及其受体FGFR2及血管内皮标记因子CD34的表达状态,并根据CD34染色计数微血管密度。结果：bFGF和FGFR2免疫组化阳性反应在寻常型进行期银屑病皮损的表皮基底层和棘层表达。显著高于正常皮肤（P〈0.01）;寻常型进行期银屑病皮损真皮浅层微血管密度显著高于正常人,该处微血管bFGF的表达也明显高于正常人（P〈0.01）,且与微血管密度（MVD）呈正相关,P〈0.01,而FGFR2在银屑病真皮浅层微血管和正常人则无显著性差异（P〉0.05）。结论：bFGF可能通过FGFR2作用在基底层和基底上层,对角质形成细胞的增殖、分化起一定作用,bFGF亦可能在银屑病真皮浅层微血管异常增殖中起一定的作用。     

Serotonin in human allergic contact dermatitis. An immunohistochemical and high-performance liquid chromatographic study

Abstract Allergic contact dermatitis (ACD) is a common clinical condition leading to considerable morbidity. We have recently demonstrated that ketanserin, a serotonin antagonist, significantly inhibits nickel sulphate-induced ACD. Furthermore, serotonin-immunoreactive (IR) cells have previously been demonstrated in normal human cutaneous melanocytes. To further elucidate the role of serotonin in cutaneous contact hypersensitivity, we compared ACD involved skin and uninvolved skin from nickel-allergic patients, and normal skin from healthy volunteers, for the presence of serotonin-like immunoreactive cells using immunohistochemistry. In addition, serotonin concentrations in ACD involved and uninvolved skin were compared by high-performance liquid chromatography (HPLC). In the skin of normal healthy volunteers, the serotonin-IR cells were situated in the basal layer of the epidermis. In uninvolved skin the cells were also situated in the basal layer, but they were more numerous and the immunofluorescence intensity was greater. In involved skin, the IR cells were fewer and they were found higher up in the epidermis. Also, the configuration of these cells was different: they showed enlarged and elongated dendrites as well as dendritic spines. The serotonin antiserum-labelled cells in ACD involved skin were also NKI-beteb positive (the latter is known as a reliable marker of melanocytes). The concentration of serotonin in involved skin was significantly higher than that in uninvolved skin in ACD patients (P < 0.05). Taken together, our previous and present results indicate that serotonin plays an important role in ACD. The basal epidermal serotonin-IR cells are more dendritic in ACD, and are found more superficial in the epidermis, where they might release their content of serotonin, thereby influencing the inflammatory process. Received: 7 July 1997 / Received after revision: 16 December 1998 / Accepted: 22 December 1998     

Studies of cell and organ culture of psoriatic and normal epidermis in vitro

Involved and noninvolved epidermis from 15 psoriatic patients, and epidermis from 12 normal individuals were grown under various conditions in vitro as cell and organ cultures. In the organ cultures of normal or noninvolved psoriatic skin, epidermal cells migrated around the dermis and differentiated. In psoriatic organ cultures, progressive necrotic changes were observed in the spinous cells including gradual detachment of the spinous layer from the dermis. In spite of these necrotic changes, newly-grown basal cells which appeared on the dermal tissue in the 9 to 12-day psoriatic explants clearly incorporated ³H-thymidine into nuclear DNA. By electron microscopy these cells were observed to have numerous ribosomes, a few mitochondria, tonofilament-like structures in the cytoplasm, and no hemi-desmosomes. Dissociated epidermal cells from the involved psoriatic skin failed to grow on plastic dishes. When these cells were plated on dishes coated with increasing amounts of collagen, the rate of cellular attachment was proportional to the thickness of the collagen coating, but they were unable to grow and form epidermal monolayers. In contrast, normal and noninvolved psoriatic epidermal cells attached to the dishes regardless of the presence of collagen and formed differentiated epidermal monolayers.     

The effect of overweight and obesity on psoriasis patients in Chinese Han population: a hospital‐based study

Background Accumulating evidence indicates that psoriasis is associated with increased risk of overweight and obesity. However, few studies have investigated this relationship in Chinese Han population. Objective The aim of this study was to explore the relationship between overweight/obesity and psoriasis and to evaluate the overweight/obesity effect on the clinical features of psoriasis in Chinese Han population. Methods A hospital‐based study was conducted, which involved in 4452 patients and 1166 controls of Chinese Han through epidemiological investigation. Controls used in the study were individuals without psoriasis from health examination centre, and other skin disease patients from outpatient department. Results Compared with the control group, a significantly greater prevalence of overweight and obesity was observed in psoriasis patients. The estimated ORs were 1.301 (95% CI, 1.105–1.531) and 1.680 (95% CI, 1.134–2.491) respectively. The disease severity of psoriasis measured by psoriasis area and severity index (PASI) was statistically correlated with body mass index (BMI) (r = 0.184, P < 0.01). Moreover, a high proportion of overweight patients had affected hands or/and feet, buttocks, trunk, legs, arms and arthritis (P < 0.01). Conclusions Our study suggested that psoriatic patients have a higher prevalence of overweight and obesity compared with non‐psoriatic patients in Chinese Han population. Overweight and obesity has different risk effect on severity and manifestations of psoriasis and might be useful for better evaluating psoriasis clinically.     

Expression of the T-cell activation antigens CD27 and CD28 in normal and psoriatic skin

Activated T lymphocytes are thought to be involved in the pathogenesis of psoriasis. From studies with peripheral blood T lymphocytes it is known that T cells show a decrease in membrane expression of CD27 molecules during continuous antigenic stimulation. The T-cell activation molecule CD28 is thought to be involved in the transduction of an antigen-non-specific costimulatory signal. Therefore, in order to elucidate further the pathogenesis of psoriasis we studied the expression of CD27 and CD28, together with CD4, CD8 and CD45RA in this benign inflammatory dermatological disease. We used immunohistochemical techniques to determine absolute numbers of T lymphocytes and expression of these T-cell activation and T-subset-specific molecules in normal (n= 7), uninvolved perilesional (n= 7) and lesional psoriatic (n= 7) skin. We found that not only lesional but also clinically uninvolved perilesional skin showed an increased number of T cells. Further, immunohistochemical studies showed that CD27 is expressed by a minority of normal skin T cells, while in lesional psoriatic skin, expression was even lower, and almost absent in perilesional skin sections. In contrast to normal skin, both perilesional and lesional psoriatic skin contained no CD28 positive T cells. In lesional psoriatic skin, however, T cells showed predominantly the CD4 phenotype, while in perilesional skin CDS positive T cells were dominant. Two conclusions were reached: first, the absolute number of T cells, their CD27, CD28 and CD45RA expression, and the influx of CD8 positive T cells, indicate that perilesional psoriatic skin is different from normal and lesional psoriatic skin; and secondly, the data on CD27 and CD28 suggest that not only lesional but also perilesional psoriatic skin is subject to continuous antigenic stimulation, thus leading to decreased CD27 and CD28 expression on skin T cells.