Blood Of Atopic Dermatitis Patients Research Articles

Granzyme B: A novel therapeutic target for treatment of atopic dermatitis.

Granzyme B is a serine protease that can play multiple roles in intracellular and extracellular perforin-dependent or non-perforin-dependent mechanisms. Granzyme B has been found to be an important factor involved in the pathogenesis of atopic dermatitis and is increased in both skin lesions and peripheral blood of atopic dermatitis patients. In this article, we review the correlation between granzyme B and atopic dermatitis to provide a novel therapeutic targeting option for clinical treatment of the latter.

Atopic Dermatitis: The Fate of the Fat.

Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease in which dry and itchy skin may develop into skin lesions. AD has a strong genetic component, as children from parents with AD have a two-fold increased chance of developing the disease. Genetic risk loci and epigenetic modifications reported in AD mainly locate to genes involved in the immune response and epidermal barrier function. However, AD pathogenesis cannot be fully explained by (epi)genetic factors since environmental triggers such as stress, pollution, microbiota, climate, and allergens also play a crucial role. Alterations of the epidermal barrier in AD, observed at all stages of the disease and which precede the development of overt skin inflammation, manifest as: dry skin; epidermal ultrastructural abnormalities, notably anomalies of the lamellar body cargo system; and abnormal epidermal lipid composition, including shorter fatty acid moieties in several lipid classes, such as ceramides and free fatty acids. Thus, a compelling question is whether AD is primarily a lipid disorder evolving into a chronic inflammatory disease due to genetic susceptibility loci in immunogenic genes. In this review, we focus on lipid abnormalities observed in the epidermis and blood of AD patients and evaluate their primary role in eliciting an inflammatory response.

Vascular inflammation in moderate‐to‐severe atopic dermatitis is associated with enhanced Th2 response

In atopic dermatitis (AD), some studies have shown an association with increased cardiovascular disease in certain populations. However, other investigations found modest or no association. Despite conflicting results, molecular profiling studies in both AD skin and blood have demonstrated upregulation of atherosclerosis and cardiovascular risk-related markers. However, the underlying mechanisms connecting AD to vascular inflammation/atherosclerosis are unknown. In this study, we aim to determine factors associated with vascular inflammation/atherosclerosis in AD patients. We used 18-FDG PET-CT to characterize vascular inflammation in AD patients and healthy subjects. In parallel, we assessed their skin and blood immune profiles to determine AD-related immune biomarkers associated with vascular inflammation. We also assessed levels of circulating microparticles, which are known to be associated with increased cardiovascular risk. We found significant correlations between vascular inflammation and Th2-related products in skin and blood of AD patients as well as atherosclerosis-related markers that were modulated by dupilumab. Circulating levels of endothelial microparticles were significantly higher in severe AD patients and tended to correlate with vascular inflammation assessed by PET-CT. Vascular inflammation in AD is associated with enhanced Th2 response and clinical severity, which may explain cardiovascular comorbidities observed in select AD populations. Larger prospective studies are needed to further evaluate vascular inflammation and cardiovascular events and mortality in AD patients. Finally, as dupilumab treatment demonstrated significant modulation of atherosclerosis-related genes in AD patients compared to placebo, these data suggest that modulation of vascular inflammation with systemic treatment should be explored in patients with AD.

Therapeutic New Era for Atopic Dermatitis: Part 1. Biologics.

Atopic dermatitis (AD) is a chronic, inflammatory cutaneous disease driven by immune dysregulation and skin barrier dysfunction. We are currently experiencing a new era of understanding of the pathogenesis of AD and, as a consequence, a new era of innovation in therapeutics, including small molecules and biologic therapy. Recently, advances in translational research have challenged the traditional AD pathogenesis paradigm of AD being solely a Th2-dominant disease. Other immune pathways seem to play a role in the complex AD pathophysiology, although the clinical relevance of these additional immune pathway abnormalities is unclear. Type 1, type 22, and type 17 pathway activation (with related cytokines/chemokines) have been demonstrated in the skin and blood of AD patients. Type 2 (interleukin [IL]-4, IL-13), IL-31, and type 22 (IL-22) pathway cytokines are increased in AD acute lesions. IL-22 induces both an epidermal hyperplasia at the onset of acute AD and a marked increase in the terminal differentiation S100 genes. This understanding of pathogenesis corresponds to a historic increase in therapeutic development in AD. The extreme clinical heterogeneity and the chronic progression of AD establish the need for newer, safer, and more effective treatments, control the disease, and improve the quality of life of affected patients.

701 High dimensional peripheral blood immune cell profiling of atopic dermatitis patients unveiled IL21 cytokine activation

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease affecting 7% of adults in the United States. While skin and blood profiling of AD primarily highlighted its Th2/ -skewing, novel Th2-targeting strategies are able to induce clearance in <40% of moderate-to-severe patients. To expand upon the current knowledge on the systemic immune activation of AD, we measured the frequencies of 13 cytokines, 4 transcription factors and activation markers in circulating skin-homing (CLA+) and systemic (CLA-) CD4+/CD8+ activated T-cell subsets using mass cytometry or CyTOF, that allows simultaneous profiling of more than 40 markers. High profiling mass cytometry enabled us to measure not only the defining Th/Tc cytokines Th/c1/IFN-g/Th/c2/IL-13/Th/c17/IL-17A/Th/c22/IL-22,Th/c/IL-9 in CD4+/CD8+ T-cells but also TNFa/GM-CSF/IL-2/IL-4/IL-5/IL-31/IL-10/IL-21 producing T cells in blood of moderate-to-severe AD patients (n=20) and controls (n=15). These cytokine-producing T-cell subsets were also highly correlated with disease severity (SCORAD). In addition to the Th2/Tc2 and Th22/Tc22 polarization, the blood of AD patients was characterized by significant increases in IL21 producing CD4+/CD8+ T-cells (p<0.01) in both CLA+/CLA- compartments. IL-21 production was primarily detected among Th/c2 and Th/c22 in AD but not in control subjects, as well as in a unique population that mainly produces IL-21. Positive correlations with SCORAD were observed in CLA+IL21+CD4+/CD8+ T cells (r=0.61; p<0.01). The frequency of these CLA+IL21+CD4+/CD8+ T cells was also correlated with that of the CLA+Th/c2/Th/c22 cells (p<0.001), suggesting the Th/c2/Th/c22 as potentially the source of IL21 in AD. In conclusion, high dimensional profiling of peripheral blood with mass cytometry revealed a possible role of systemic IL21-skewing in moderate-to-severe AD.

Expression of ergotope-associated markers of T lymphocytes in atopic dermatitis after in vitro polyclonal activation

The antiergotypic response leads to the formation of effector T cells able to eliminate activated lymphocytes independently of their antigenic specificity, since the targets of these cells are molecules produced during cell activation (ergotopes). In this paper, we describe the level of expression of the ergotope-associated markers CD25, HSP60, and HLA-DR by the T lymphocytes isolated from the blood of atopic dermatitis patients immediately after isolation and after cultivation. After 10-day cultivation in the presence of anti-CD3 antibodies and IL-2, the expression levels of early and late activation markers in T cells have changed: the shares of CD25-positive CD4+ and CD8+ lymphocytes increase to 68 and 47%, respectively, and the share of HLA-DR-positive cells increases to 26 and 33%. The density of HLA-DR molecules on the surface of activated T cells increases more than fivefold. Almost all T cells before and after cultivation express 60 kDa heatshock protein (HSP60); however, the CD4+ cells activated in vitro contain more HSP60 molecules than do the in vitro-activated CD8+ cells and the CD4+ cells of peripheral blood. Thus, the T cells of atopic-dermatitis patients have the status of activated cells because they express sufficient amounts of early and late activation markers; presumably, they can enhance the induction of antiergotypic response when administered to patients. Taking into account that antiergotypic regulation acts on activated T cells independently of their antigenic specificity, immunotherapy utilizing autologous activated T lymphocytes can be of interest as a method for targeted action on pathogenetic components of atopic dermatitis.

Up-regulated expression of substance P in CD8+ T cells and NK1R on monocytes of atopic dermatitis

BackgroundLarge numbers of CD8+ T cells were observed in atopic dermatitis (AD) skin, and monocytes from AD patients showed increased prostaglandin E2 production. However, little is known about the expression of substance P (SP) and its receptor NK1R in blood leukocytes of patients with AD.ObjectiveTo explore the expression of SP and NK1R in leukocytes of AD and the influence of allergens on SP and NK1R expression.MethodsThe expression levels of SP and NK1R in patients with AD were examined by flow cytometry, ELISA and a mouse AD model.ResultsThe plasma SP level was 4.9-fold higher in patients with AD than in HC subjects. Both the percentage of SP expression in the population and mean fluorescence intensity (MFI) of SP expression were elevated in CD8+ T cells in the blood of AD patients. However, both the CD14+NK1R+ population and MFI of NK1R expression on CD14+ cells were enhanced in the blood of AD patients. Allergens ASWE, HDME and PPE failed to up-regulate SP expression in CD8+ T cells. However, allergens ASWE and HDME both enhanced NK1R expression on CD14+ blood leukocytes regardless of AD or HC subjects. OVA-sensitized AD mice showed an elevated proportion and MFI of SP-expressing CD8+ T cells in the blood, which agrees with the SP expression situation in human AD blood. Injection of SP into mouse skin did not up-regulate NK1R expression on monocytes.ConclusionsAn elevated plasma SP level, up-regulated expression of SP and NK1R indicate that the SP/NK1R complex is important in the development of AD. Therefore, SP and NK1R antagonist or blocker agents may help to treat patients with AD.Trial registration Registration number: ChiCTR-BOC-16010279; Registration date: Dec., 28, 2016; retrospectively registered

Expression and significance of peripheral blood T helper cell 22 in patients with atopic dermatitis

[Objective]To detect the expression of peripheral blood T helper cell 22 (Th22) in patients with atopic dermatitis (AD),and approach its role in AD pathogenesis.[Methods]The patients' conditions were evaluated by Eczema area and severity index (EASI) score.The peripheral blood Th22 (IL-22) cells of 46 patients with AD and 28healthy controls were detected by flow cytometry..Serum 1L-22,IFN- γ and IL-4 level were detected by ELISA assay.[Results]Th22 cells in peripheral blood of AD patients (2.35 ± 0.64)％ were significantly higher than those in the control group (0.94 ± 0.43)％ (P＜ 0.01).There was a positive correlation between Th22 cells and serum IL-22 (r=0.48,P ＜ 0.05) and no correlation between Th22 cells and IFN- γ,IL-4 (r=0.105,r=-0.267,P＞ 0.05),Th22 cells and EASI score of the disease was positively correlated (r=0.53,P ＜ 0.05).[Conclusion]Th22 cells may be used as the index of monitoring AD severity or disease fluctuations. Key words: Atopic dermatitis; Peripheral blood; T helper cell 22

CRTH2 is Critical to the Development of Colitis Induced by Dextran Sodium Sulfate (DSS)

Chemoattractant Receptor-homologous molecule expressed on Th2 cells [CRTH2] is expressed on granulocytes (eosinophils, basophils and neutrophils), Th2 cells and monocytes. CRTH2 has been implicated in the development of cutaneous inflammation as CRTH2+ CD4+ T cells and CRTH2+ eosinophils are increased in the blood of atopic dermatitis patients. CRTH2 is also up-regulated in circulating neutrophils of psoriatic patients. Interestingly, CRTH2 is detected in the mucosa of patients with Inflammatory Bowel Disease (IBD) ulcerative colitis, where the CRTH2 positive cells localize within and adjacent to regions of inflamed mucosa suggesting that CRTH2 may play a role in IBD. However, the exact downstream inflammatory pathways resulting from CRTH2 activation in colitis are not well characterized. To gain a better understanding of the effects of CRTH2 activation in the pathogenesis of colitis, we have generated a small molecule inhibitor against CRTH2 and its potency was first validated in an oxazolone induced contact dermatitis model. We investigated the consequences of inhibiting CRTH2 in the development of IBD using a Dextran Sodium Sulfate (DSS)-induced colitis mouse model. Compared to the vehicle control group, mice treated with a selective CRTH2 antagonist had reduced disease severity as measured by weight loss, as well as serum acute phase protein, haptoglobin. Furthermore, pro-inflammatory cytokine gene expression for TNFα, IL-1β, IL-6, IL-17A, and IFNγ were reduced in colons of mice that had been treated with the CRTH2 antagonist compared with DSS treated controls that received vehicle. Taken together, our data identify a previously unrecognized role for CRTH2 in the initiation/amplification and/or stabilization of colon inflammation.

Local and systemic immune response in patients withsevere atopic dermatitis

Background. to comparatively investigate cytokine gene expression in the skin and peripheral blood of atopic dermatitis (AD) patients and healthy individuals. Methods. Samples of skin and peripheral blood from 48 severe AD patients SCORAD (Scoring Atopic Dermatitis) 78,5 [57; 89], IGA (Investigators Global Assessment) 4,2 [3,9; 4,7]) at the age of 17 to 45 years and 20 healthy donors aged from 19 to 32 years were analyzed for gene expression of cytokines using real time reverse transcription polymerase chain reaction (RT-PCR). Results. In the skin of patients with AD, a significant increase of the level of gene expression was observed for interleukin IL2R (interleukin) (р=0,0023), IL5 (р=0,002), IL6 (р=0,0023), IL8 (р=0,01), IL12β (р=0,0023), IL10 (р=0,0023), IL23 (р=0,002), IL29 (р=0,0023), and TGFβ (transforming growth factor) (p=0,0023) as compared to healthy individuals. In contrast, no difference between AD patients and healthy donors was detected with respect to cytokine gene expression in the peripheral blood. Conclusions. Activity of IL-2R, IL-8, IL-12β, IL-23, IL-29, and TGFβ that are markers of chronic inflammation and Th1 immune response in severe AD and IL-5, IL-10 that are anti-inflammatory cytokines and markers of Th2 response was predominant in the skin but not in the blood of AD patients.

THE INFLUENCE OF TOPICAL GLUCOCORTICOSTEROIDS ONCYTOKINE GENE EXPRESSION IN THE SKIN AND PERIPHERALBLOOD OF ATOPIC DERMATITIS PATIENTS

Background. To investigate the influence of mometasone furoate 0,1% cream on cytokine gene expression in the skin and peripheral blood of atopic dermatitis (AD) patients comparing with control. Material and methods. 40 AD patients were included in the study and divided into 2 groups. group 1 patients were given continuous course of mometasone furoate 0,1% cream treatment for 14 days. group 2 patients were given indifferent emollient elobase cream for 14 days. Clinical efficacy of the treatment was assessed on the following features: SCORAD index, Investigators global Assessment (IgA) score and subjective assessment of itch and dryness of the skin according to skin area to be studied. Skin samples and peripheral blood of atopic dermatitis were used as material for immunological study. Interleukin (IL)1B, IL2, IL2r, IL4, IL5, IL6, IL7, IL8, IL10, IL 12A, IL12B, IL15 (total), IL15 , IL17A, IL18, IL23, IL28, IL29, Interferon (IFN)-ƒ, Tumor necrosis factor (TNF), Transforming growth factor beta 1 (TGFB1), forkhead box P3 (FOXP3) gene expression were defined in the skin and peripheral blood of AD patients by realtime reverse transcription polymerase chain reaction (RT-pCR). Results. positive clinical effect was found with all AD patients on the mometasone furoate 0,1% cream therapy background for 14 days and also dryness, rushes and skin itch decreased. Stаtistical significant decrease of proinflammatory cytokines IL2, IL2r, IL5, IL8, IL12В, IL23, IFN-ƒ gene expression was marked. They are the markers of chronic inflammation and Th1 immune response. Studying peripheral blood after mometasone furoate 0,1% cream treatment increase of TGFB1, FOXP3 gene expression level was found. no significant changes of cytokine gene expression in AD patients, who got elobase cream were found. Conclusion. Antiinflammatory activity of mometasone furoate 0,1% cream was shown by its influence on proinflammatory cytokines IL2, IL2r, IL5, IL8, IL12В, IL23, IFN-ƒ gene expression in the skin and mechanisms of immune response in moderate and severe AD patients.

Cytokine gene expression in the skin and peripheral blood of atopic dermatitis patients and healthy individuals

OBJECTIVES: Atopic dermatitis (AD) is an increasingly common, chronic, relapsing, inflammatory skin disease characterized by impaired epidermal barrier function and cutaneous inflammation. The prevalence of AD has steadily increased during the past few decades. The aim of this study was to comparatively investigate cytokine gene expression in the skin and peripheral blood of atopic dermatitis patients and healthy individuals. RESULTS: In the skin of patients with AD, a significant increase of the level of gene expression was observed for interleukin (IL)-2r (p < 0.0023), IL-5 (p = 0.002), IL-6 (p < 0.0023), IL-8 (p = 0.01), IL-12B (p < 0.0023), IL-10 (p < 0.0023), IL-23 (p = 0.002), IL-29 (p < 0.0023), and transforming growth factor beta (tGFbeta) (p < 0.0023) as compared to healthy individuals. In contrast, no difference between AD patients and healthy donors was detected with respect to cytokine gene expression in the peripheral blood. METHODS: Samples of skin and peripheral blood from 48 severe AD patients (SCORAD = 78.5 [57;89], IGA = 4.2 [3,9;4,7]) at the age of 17 to 45 years and 20 healthy donors aged from 19 to 32 years were analyzed for gene expression of cytokines using real-time reverse transcription polymerase chain reaction (RT-PCR). CONCLUSIONS: Activity of markers of chronic inflammation and Th1 immune response in severe AD, namely IL-2r, IL-8, IL-12B, IL-23, IL-29 and TGFbeta, as well as activity of anti-inflammatory IL-5 were predominant in the skin but not in the blood of AD patients.

Topical immunotherapy influence on citokins genes expression in skin and blood in atopicdermatitis patients

Background. To study the clinical effectiveness of topical immune modulator cream thymogen 0,05% and its influence on some immunological parameters in the skin and blood of atopic dermatitis (AD) patients. Materials and methods. 40 people were included in the study, who were divided into main (AD patients, n=20) and a control group (healthy donors, n=20). All AD patients received topical treatment with cream thymogen 0,05% during 14 days. Patients applied cream to affected skin 2 times daily. Clinical efficacy of the treatment was assessed by changes of following parameters: investigated global assessment (IGA), subjective evaluation of the itch intensity and skin dryness . Samples of skin biopsies and peripheral blood of AD patients and healthy donors were tested for gene expression of cytokines by polymerase chain reaction in real time. Results. Topical treatment with cream thymogen 0,05% during 14 days in all AD patients showed positive clinical effect: reduction of dryness and itch. Immunological analysis revealed a significant increasing of cytokine IL-7 gene expression and decreasing of cytokines IL-8, IL-5 genes expression (p

Human tissue kallikrein expression in the stratum corneum and serum of atopic dermatitis patients

Human tissue kallikreins are a family of 15 trypsin- or chymotrypsin-like secreted serine proteases (KLK1-KLK15). Many KLKs have been identified in normal stratum corneum (SC) and sweat, and are candidate desquamation-related proteases. We report quantification by enzyme-linked immunosorbent assay (ELISA) of KLK5, KLK6, KLK7, KLK8, KLK10, KLK11, KLK13 and KLK14 in the SC and serum of atopic dermatitis (AD) patients by ELISA, and examine their variation with clinical phenotype, correlation with blood levels of eosinophils, lactate dehydrogenase (LDH) and immunoglobulin E. The overall SC serine protease activities were also measured. In the SC of AD, all KLKs, except KLK11, were significantly elevated. The elevation of chymotrypsin-like KLK7 was predominant, compared with trypsin-like KLKs. The SC overall plasmin- and furin-like activities were significantly elevated, while trypsin- and chymotrypsin-like activities did not differ significantly. In the serum of AD patients, KLK8 was significantly elevated and KLK5 and KLK11 were significantly decreased. However, their serum levels were not modified by corticosteroid topical agents. The alterations of KLK levels in the SC of AD were more pronounced than those in the serum. KLK7 in the serum was significantly correlated with eosinophil counts in the blood of AD patients, while KLK5, KLK8 and KLK11 were significantly correlated with LDH in the serum. In conclusion, we report abnormal kallikrein levels in the SC and the serum of AD patients. KLKs might be involved in skin manifestation and/or focal/systemic inflammatory reactions in AD. Our data may contribute to a better understanding of the pathogenesis of AD.

Circulating CD4+T Cells with Skin-homing Properties in Atopic Dermatitis

901 Circulating CD4+T Cells with Skin-homing Properties in Atopic Dermatitis G. N. Drannik1, A. I. Kurchenko1, L. M. DuBuske2; 1Dept. Clinical Immunology and Allergology, National Medical University, Kiev, UKRAINE, 2Immunology Research Institute of New England, Gardner, MA. RATIONALE: Atopic dermatitis (AD) is characterized by the influx of activated T cells into skin lesions, determined by expression of cutaneous lymphocyte-associated antigen (CLA). This study assesses the number of circulating CLA+T cells in blood of AD patients. METHODS: 35 patients ( 25 years of age) with chronic AD were examined. The diagnosis was based on the criteria of Hanifin and Rajka. All patients had positive allergy skin prick tests. Peripheral blood T cell subpopulation was analyzed by direct immunofluorescence. Flow-cytometry was performed with an EPICS XL (Coulter). RESULTS: CLA expression of peripheral blood T cells of both AD patients and healthy subjects revealed that the share of T cells with CLApositivity was greater among the subpopulation of CD4+Tcells than among CD8+T cells. In the subpopulation of CD4+T cells, the number of cells that express CLA was significantly greater in blood of AD patients (29.3±3.4%) when compared with healthy subjects (11.5±2.4%), but there were no significant differences in levels of CLA+CD8+ cells (AD 5.3±1.4 % versus healthy subjects 4.4±2.3%). CLA+CD4+T cells but not CLA+CD8+ T cells are expanded and predominate in the peripheral blood of AD patients. CONCLUSIONS: The influx and accumulation of T cells in AD inflamed skin is maintained by the activation of production of specific J ALLERGY CLIN IMMUNOL Abstracts S233 VOLUME 117, NUMBER 2

Cytokine network and dysregulated apoptosis in atopic dermatitis

Activation and skin-selective homing of peripheral blood memory/effector T cells and effector functions in the skin represent sequential immunological events in the pathogenesis of atopic dermatitis (AD). T cells infiltrating the skin utilize the cutaneous lymphocyte-associated antigen (CLA) and other receptors to recognize and cross the vascular endothelium. In the peripheral blood of AD patients, both CD4+ and CD8+ subsets of CLA+CD45RO+ T cells are in an activated state with high CD25, HLA-DR, and CD40- ligand expression. They express upregulated Fas and Fas-ligand and undergo activation-induced apoptosis. After homing to skin these T cells form dermal infiltrates which play a key role in the pathogenesis of the disease. Skin-infiltrating T cells in AD are protected from activation-induced cell death, although they express both Fas and Fas-ligand. They are protected from apoptosis by cytokines such as IL-2, IL-4, and IL-15 and extracellular matrix components such as fibronectin and transferrin. CLA+, skin-homing T cells may play a role in peripheral blood eosinophilia and hyper IgE production by high IL-5 and IL-13 expression, respectively. These T cells secrete IFN-γ in the skin, which upregulates Fas on keratinocytes and renders them susceptible to apoptosis. Keratinocyte apoptosis is induced by Fas-ligand, either soluble or expressed on the surface of T cells, leading to eczema formation. Here we discuss the mechanisms of skin-selective T cell homing and activation, and emphasize the concept of dysregulated apoptosis of T cells, eosinophils, and keratinocytes as essential pathogenetic episodes in AD and other eczematous disorders.

Expression of cutaneous lymphocyte-associated antigen on human CD4(+) and CD8(+) Th2 cells.

The cutaneous lymphocyte-associated antigen (CLA) represents the homing receptor involved in selective migration of memory/effector T cells to the skin. Numerous reports demonstrated distinct CLA expression on Th1 cells. However, T cells isolated from skin lesions and CLA(+) T cells circulating in peripheral blood of atopic dermatitis patients expressed high IL-5 and IL-13. Accordingly, we investigated the regulation of CLA on human type 1 and type 2 T cells. CLA was induced on freshly generated Th1 and Tc1 cells only, but not on those of type 2. Anti-CD3 stimulation was sufficient to induce CLA on Th2 cells in the absence of serum in the culture medium. In serum containing medium, IL-4 inhibited CLA and related alpha-fucosyltransferase mRNA expression. IL-12 and/or staphylococcal enterotoxin B (SEB) stimulation up-regulated CLA expression on either Th2 and Tc2 cells. On stimulation with IL-12, CLA was expressed on the surface of bee venom phospholipase A(2)-specific Th1, Th2, Th0 and T regulatory 1 clones, representing non-skin-related antigen-specific T cells. In addition, CLA could be re-induced on T cells that had lost CLA expression upon resting. These results suggest that skin-selective homing is not restricted to functional and phenotypic T cell subsets.

CD30 expression on circulating memory CD4+ T cells as a Th2-dominated situation in patients with atopic dermatitis.

Th2 clones have been reported to express CD30 preferentially, but whether T cells producing Th2-type cytokines may favor CD30 expression in the in vivo state remains unknown. We investigated the expression of CD30 on circulating T cells in atopic dermatitis (AD) as a Th2-dominated disorder. Peripheral blood mononuclear cells were prepared from 51 AD patients and 14 nonatopic controls, and their phenotypes were analyzed with flow cytometry. Cytokine production by stimulated CD4+ T cells was also assessed by the single-cell-staining method. Flow cytometric analysis clearly revealed that CD30+ T cells were identifiable in the blood of AD patients with greater frequency compared to controls. The important finding was that CD30 expression was restricted to a small but substantial population of memory (CD45RO+) CD4+ T cells, but not CD8+ ones. In AD patients, it was demonstrated that the percentages of CD30+ cells within CD45RO+ CD4+ T cells correlated well with the disease severity, serum IgE levels, peripheral eosinophil counts, and tendency toward Th2-dominant cytokine pattern as determined by the ratio of interleukin-4 to interferon-gamma production. This study suggests that CD30 expression in circulating T cells might serve as an in vivo marker for the Th2-dominated condition.