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Notes: In situ lymphocyte subsets in 12 patients with patchy alopecia areata or alopecia universalis were estimated using monoclonal antibodies and immunoperoxidase technique. The majority of the inflammatory cells around the hair bulbs and follicles where leu 4+ T-cells with the subphenotypes of either leu 2a+ (suppressor/cytotoxic T-cells) or leu 3a+ (helper/inducer T-cells). Many of the T-cells expressed HLA-DR class II antigen. In about half of the patients, the hair bulbs and follicles were also infiltrated with T-cells.Eight of the 12 patients were treated with dinitroch-loro-benzene. Six of these patients were biopsied during treatment. The number of T-cells around the hair bulbs and follicles increased during; treatment and niam T-cells were seen in the hair bulbs and follicles. In five of the six patients treated with dinitrochlorobenzene, an increase in the percentage of leu 2a+ cells around the bulbs and follicles was noticed. The increase in leu 2a+ cells may be of importance for the DNCB-induced re-growth of hair.

Notes: The clinical, histological, phenotypic and genotypic features of 21 primary cutaneous B-cell lymphomas (CBCLs) have been investigated. The patients were 13 men and eight women aged 34–91 years (median 67) at diagnosis. Eighteen patients had localized disease, and three had multiple skin lesions at diagnosis. Twelve patients developed cutaneous or extracutaneous recurrences, and five died from malignant lymphoma 7–84 months (median 36) after diagnosis. Histological examination showed features of marginal zone/mucosa-associated lymphoid tissue (MALT)-type lymphoma in 12 cases. Three of these had transformed to diffuse large B-cell lymphoma (DLBCL) in relapse biopsies. The remaining cases were seven primary DLBCLs and two cases tentatively classified as follicle centre cell (FCC) lymphoma. The neoplastic B cells showed similar phenotypes and genotypes in most cases (CD20+, CD79+, CD5–, CD10–, cyclin D1–, bcl-2+, bcl-x–, bax–, t(14;18)-negative). p53 protein was expressed in five cases, and four harboured mis-sense or loss-of-function mutations in the p53 gene. Deletion or promoter region hypermethylation of the p16INK4a gene was detected in two patients with DLBCL. The level of retinoblastoma protein expression and the proliferative fraction were significantly higher in DLBCL (〉 50%) than in MALT- or FCC-type lymphomas (〈 10%). Features associated with an unfavourable prognosis were the presence of multiple skin lesions at diagnosis, transformation from MALT-type lymphoma to DLBCL, and possibly p16INK4a aberrations. It is concluded that most CBCLs are dissimilar from FCC lymphomas and seem to be more closely related to marginal zone/MALT-type lymphomas. It is also suggested that there are fundamental differences between DLBCL and other histological categories of CBCL, indicating that cutaneous DLBCL is a separate entity with an increased growth potential and genetic features similar to DLBCL originating in other anatomical sites.

Notes: Summary In this study we tested the capacity of ultraviolet B (UVB)-irradiated major histocompatibility complex (MHC) class II+ keratinocytes, monocytes and dendritic cells to activate T cells in the presences of Staphylococcus enterotoxin B. We demonstrated that UVB irradiation of MHC class II+ keratinocytes does not change their capacity to activate T cells in the presence of Staphylococcus enterotoxin B. In contrast. UVB irradiation of antigen T cells after UVB irradiation was not due to factors relased form UVB-irradiated cells. The interferon-γ induced uupregulation of HLA-DR and intercellular adhesion molecule-l on accessory cell function of interferon-γ pretreated monocytes. Differential requirements for and UVB regulation of costimulatory molecules may be involved. Since blocking of the B7/CD28 pathway affects the capacity of dendritic cells but not keratinocytes to activate T cells in the presence of Staphylococcus enterotoxin B. Thus. MHC class II+ keratinocytes in the presence of superantigens released from staphylococci may activate T cells and maintain inflammation despite UVB treatment.

Notes: Despite the critical role of the Langerhans cells in the induction of contact hypersensitivity reactions, non-Langerhans antigen-presenting cells in already sensitized individuals may play a role in the elicitation phase of a contact hypersensitivity reaction, following epicutaneous challenge with antigens, the number of CD1+ DR+ epidermal Langerhans cells increased in a time-dependent way and. concomitantly. CD1−OKM5+ DR+ epidermal non-Langerhans cells appeared. In parallel with this, the capacity of epidermal cells to present both alloantigens and auto, nominal antigens increased, and 4 days after initiation of the contact hypersensitivity reactions 33–53% of the epidermal antigen-presenting capacity was due to CD1− non-Langerhans antigen-presenting cells. Thus, contact hypersensitivity skin reactions are accompanied by the appearance of non-Langerhans antigen-presenting cells capable of presenting both alloantigens and auto/nominal antigens.

Notes: This study investigated the phenotype and function of different antigen-presenting cells (APC) present within the epidermis of patients with cutaneous T-cell lymphoma (CTCL). Involved epidermis of CTCL compared with uninvolved was found to contain increased numbers of CDI + DR+ APC. This population was heterogeneous and comprised both leucocytes of a novel CD1+DR+CD36 (OK.M5)+ phenotype and CD1+DR+CD36− indeterminate/Langerhans cells. The CD1+DR+CD36+ leucocytes did not express TcR-1, CD5, CD 15. or CD22, and only a minor population expressed CD11, demonslrating that they were neither T nor B cells, and did not belong lo the major CD11+ (OKM1+) blood monocyte population. Electron microscopy of purified CD36+ lesional epidermal cells (EC) demonstrated that they lacked Birbeck granules found on CD1+-selected Langerhans cells, and most cells exhibited features of indeterminate cells or macrophages.The capacity of EC from involved epidermis to present alloanttgens was found to be increased relative to uninvolved epidermis in all patients tested, and this capacity was critically dependent upon the presence of CD45+ DR+ bone marrow-derived cells but not on the presence of CD45+ DR+ keratinocytes. Positive selection using MoAb against CDI and CD36 demonstrated that both cell populations exhibited the capacity to stimulate T cells. The results indicate that a novel antigen-presenting cell population with a unique phenotype is present within involved skin of patients with mycosis fungoides. These cells express CD36 in addition to CD1 and have an ultrastructural appearance consistent with a dendritic antigen-presenting cell derivation.

Notes: CD1+ antigen-presenting cells in involved epidermis of patients with cutaneous T-cell lymphoma exhibit an enhanced functional capacity to activate autologous CD4+ T cells compared with CD1+ antigen-presenting cells from uninvolved and normal epidermis. Class II major histocompatibility complex molecules are involved in antigen presentation, and their expression on CD1+ Langerhans cells is known to vary. The expression of all three class II (HLA-DR, -DQ, -DP) molecules was therefore determined on CD1+ epidermal cells from both involved and uninvolved epidermis, using flow cytometry. The involved CD1+ epidermal cells exhibited a 1.5–1.6-fold, statistically significant increase in fluorescence intensity after staining of the class II molecules (HLA-DR, -DQ, -DP) compared with CD1+ epidermal cells from uninvolved epidermis. The autologous CD4+ T-cell activation was almost completely blocked by anti-HLA-DR, and partly by anti-HLA-DQ and anti-HLA-DP.In contrast, an antibody against class I, and an irrelevant control antibody, had no blocking effect. In a pokeweed mitogen assay it was demonstrated that autologous CD4+ T cells, activated by involved epidermal cells, demonstrated suppressor activity rather than helper activity. The suppressor activity was dependent on the presence of HLA-DR-positive epidermal cells. Thus, in cutaneous T-cell lymphoma, class II molecules on the individual CD1+ antigen-presenting cell are upregulated in clinically involved compared with uninvolved epidermis, and these molecules are crucially involved in activation of CD4+ T cells.

Notes: Summary Background To reduce the skin nickel exposure of the population the Danish Ministry of Environment issued a regulation that was implemented in 1992, and the European Union countries have recently adopted an expanded regulation. Objectives The aim of our combined patch testing and questionnaire investigation of girls in public schools and high schools/production schools was to evaluate whether the regulation has had an impact on the prevalence of nickel sensitization. Methods To find a group of girls with ears pierced mainly after implementation of the nickel-exposure regulation in Denmark, girls were recruited from the fifth and sixth grade in 12 public schools (the public school group). After the public school level almost all girls from a public school population continue their education in high schools or other schools such as production schools or technical schools. Therefore, to find girls demographically similar to the public school girls but older, and with ears pierced before implementation of the regulation, girls from seven high schools and two production schools were recruited (the high school group). Four hundred and twenty-seven girls in the public school group (mean age 12·4 years, range 10–14) and 534 in the high school group (mean age 18·8 years, range 17–22) participated. All participants filled out a questionnaire concerning ear piercing, use of oral braces and former patch testing for nickel sensitivity. Three hundred and five girls (71·4%) in the public school group and 275 (51·5%) in the high school group were patch tested or had been tested previously and the results of these tests were included in the study. The relation between the frequency of nickel sensitization and the various factors that might influence the prevalence of nickel sensitization was evaluated by multivariate logistic regression analysis. The investigation was conducted from March 1999 to March 2000. Results The study showed that both increasing age and having ears pierced before 1992 enhanced the prevalence of nickel sensitization. We found that 17·1% of the girls in the high␣school group demonstrated a positive patch test reaction to nickel. In contrast, the prevalence of nickel sensitization in the public school group was only 3·9%. Comparing girls with and without pierced ears, the prevalence of nickel sensitization was significantly higher in girls with ears pierced before, but not after, 1992 (odds ratio 3·34 and 1·20, respectively). Only in the high school group was there a tendency that wearing oral braces before ear piercing had a protective effect on nickel sensitization, but this did not reach statistical significance. Conclusions As we found an effect of ear piercing before but not after 1992, this study strongly␣suggests that implementation of the nickel-exposure regulation in 1992 in Denmark has had the intended effect of protecting the female population from becoming allergic to nickel.

Notes: The monoclonal antibody UM4D4, assigned to the CDw60 cluster of differentiation, identities an epilope expressed on a subset of normal T cells, some malignant T cells, melanocytes, malignant melanoma cells and hyperproliferative psoriatic keratinocytes. CDw60 antibodies bind to the acetylated form of GD3 gangliosides. These gangliosides have been implicated in the control of cellular proliferation. Because the acetylated form of GD3 has been demonstrated in basal cell carcinomas, we determined whether the CDw60 epitope was expressed in basal cell carcinomas (n= 24) and squamous cell carcinomas (n= 2). Biopsies of these tumours were sectioned on a cryostat, and stained with anti-CDw60 using a sensitive indirect immunoperoxidase technique. A mean of 74±4% (mean ± SEM) of the basal cell carcinoma cells expressed CDw60. In contrasl, CDw60 expression in normal skin was confined to melanocytes and a few scattered keratinocytes at the basal cell layer. CDw60 expression in basal cell carcinomas was highly upregulated at the tumour front in most of the lesions, whereas the squamous cell carcinomas showed uniform CDw60 expression in all areas.

Notes: Summary Background  Apoptosis has been proposed to act as an important mechanism for eliminating keratinocytes that have been irreversibly damaged by ultraviolet (UV) irradiation. One way to induce apoptosis in keratinocytes is through activation of the cell surface receptor Fas (CD95), either with the ligand (FasL) or directly with UV radiation. Objectives  To investigate the regulation of Fas and FasL expression in human skin and the formation of apoptotic cells after in vivo exposure to UVB or long-wave UVA radiation. Methods  Volunteers were irradiated with either 3 minimal erythema doses (MED) of UVB ( n  = 6) or 3 MED of long-wave UVA ( n  = 6) on buttock skin 12, 24 and 72 h before skin punch biopsies were taken. Expression of Fas and FasL was demonstrated by immunohistochemistry on cryostat sections. Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated fluorescein-deoxyuridine triphosphate nick-end labelling reaction. Results  In five of six subjects, exposure to UVB radiation resulted in increased homogeneous expression of Fas on epidermal cells, with greatest expression at 24 and 72 h after irradiation. In all subjects, exposure to long-wave UVA resulted in increased homogeneous expression of Fas on epidermal cells, with greatest expression at 12 h after irradiation. In five of six subjects, exposure to UVB radiation resulted in temporarily decreased expression of FasL, but after 72 h the expression of FasL had returned to the preirradiation level. The expression of FasL on epidermal cells after exposure to long-wave UVA showed considerable variation. UVB irradiation was a stronger inducer of epidermal apoptosis than was UVA irradiation. The number of apoptotic epidermal cells did not correlate with expression of Fas or FasL. Conclusions  In human skin the expression of Fas on epidermal cells increases after in vivo exposure to UVB or long-wave UVA. Exposure to UVB causes a temporary decrease in the expression of FasL on epidermal cells.

Notes: To investigate whether the overall histamine turnover is increased in patients with atopic dermatitis, without respiratory disease, the urinary excretion of the main histamine metabolite 1,4-methyl-imidazoleacetic acid (MIAA) was examined in 23 patients and in 23 age- and sex-matched non-atopic controls. The patients excreted significantly more MIAA than the controls. One third of the patients however, showed MIAA excretion within or below normal range. The MIAA excretion was neither correlated to the severity of the eczema nor to the total serum IgE. It was concluded that histamine does not play a significant role in the pathophysiology of atopic dermatitis, and that the great variation in MIAA excretion, and hence the histamine turnover, reflected the spectrum of histamine releasability in the patients.