Henning C. Dittmar
University of Freiburg
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Hautarzt | 2001
Henning C. Dittmar; Dorothee Pflieger; Erwin Schöpf; Jan C. Simon
ZusammenfassungHintergrund und Fragestellung.Über den erfolgreichen Einsatz der UVA1-Phototherapie bei der atopischen Dermatitis (AD) wurde mehrfach berichtet, allerdings mit unterschiedlichen Dosierungsschemata. Patienten/Methodik. In einer randomisierten, kontrollierten, prospektiven Pilotstudie verglichen wir bei Patienten mit akut exazerbierter atopischer Dermatitis (SCORAD>30) die Effektivität einer Therapie mit 15 Bestrahlungen einer “high dose”- (maximale Einzeldosis 130 J/cm2, maximale kumulative Dosis 1840 J/cm2), “medium dose”- (maximale Einzeldosis 65 J/cm2, maximale kumulative Dosis 975 J/cm2) oder “low dose”- (maximale Einzeldosis 20 J/cm2, maximale kumulative Dosis 300 J/cm2) UVA1. Nach Bestimmung der IPD erfolgte eine randomisierte Zuordnung zu einer der 3 Therapiegruppen. Die Patienten erhielten außer 15 Bestrahlungen 5-mal pro Woche keine weitere Therapie mit Ausnahme von pflegenden Externa. Ergebnisse. Nach 15 Behandlungen fand sich in der “high dose”- und “medium dose”-Gruppe eine statistisch signifikante Besserung des SCORAD nach Therapie. Die “low dose”-Gruppe zeigte hingegen keine signifikante Besserung des SCORAD. In keiner der 3 Gruppen zeigte sich unter Therapie eine statistisch signifikante Veränderung der IgE- und ECP-Spiegel bzw. der Anzahl der Eosinophilen im peripheren Blut. Die UVA1-Therapie zeigte bei den Patienten eine gute Akzeptanz und keine Nebenwirkungen. Schlussfolgerungen. Zur Behandlung der akuten atopischen Dermatitis eignet sich neben der “high dose”-Therapie auch ein “medium dose”-Therapieregime.AbstractBackground and Objective. UVA1 phototherapy is an new effective treatment modality for acute atopic dermatitis (AD). However there is still some controversy about the optimal UVA1 single and cumulative dose. Patients/Methods. We compared in a randomized, controlled, prospective pilot study the efficacy of a therapy with 15 treatments of a “high dose” (max. single dose of 130 J/cm2, max. cumulative dose 1840 J/cm2), “medium dose” (max. single dose of 65 J/cm2, max. cumulative dose 975 J/cm2) or “low dose” (max. single dose of 20 J/cm2, max. cumulative dose 300 J/cm2) UVA1 in patients with acutely exacerbated atopic dermatitis (SCORAD>30). After determination of the IPD, patients randomized into one of the three treatment arms. The patients received 15 treatments (5 times per week) without any additional therapy except for topical skin care. Results. After 15 treatments the “high dose” and “medium dose” groups showed a statistically significant reduction of the SCORAD. No significant reduction of the SCORAD was observed in the “low dose” group. All three treatment arms displayed no statistically significant changes in the IgE and ECP levels and in the number of eosinophils in the peripheral blood. The UVA1 therapy was well tolerated by all patients. No side effects were observed. Conclusions. This study suggests that both the “high dose” and the “medium dose” regimens are effective in the treatment of patients with acutely exacerbated atopic dermatitis.
Cell Adhesion and Communication | 1998
Johannes M. Weiss; Andreas C. Renkl; Jonathan P. Sleeman; Henning C. Dittmar; Christian Termeer; Sabine Taxis; Norma Howells; Erwin Schöpf; Helmut Ponta; Peter Herrlich; Jan C. Simon
Upon antigen encounter epidermal Langerhans cells (LC) and dendritic cells (DC) emigrate from peripheral organs and invade lymph nodes through the afferent lymphatic vessels and then assemble in the paracortical T cell zone and present antigen to T lymphocytes. Part of this process is mimicked by metastasizing tumor cells. Since splice variants of CD44 promote metastasis to lymph nodes we explored the expression of CD44 proteins on migrating LC and DC. We show that following antigen contact, LC and DC upregulate pan CD44 epitopes and epitopes encoded by variant exons v4, v5, v6 and v9. Antibodies against CD44 epitopes arrest LC in the epidermis, prevent the binding of activated LC and DC to the T cell zones of lymph nodes, and severely inhibit their capacity to induce a delayed type hypersensitivity reaction to a skin hapten in vivo. Our results demonstrate that CD44 splice variant expression is obligatory for the migration and function of LC and DC.
Photochemistry and Photobiology | 1998
Ralf W. Denfeld; Jens P. Tesmann; Henning C. Dittmar; Johannes M. Weiss; Erwin Schöpf; Hans Ulrich Weltzien; Jan C. Simon
We have reported previously that low‐dose UVB radiation (UVBR, 50‐200 J/m2) perturbs the antigen‐presenting cell (APC) function of murine Langerhans cells (LC) by interfering with yet undefined costimulatory signals. In this study, we investigated (1) the effects of UVBR on the expression of the costimulatory molecules B7‐1 and B7‐2 on murine LC, (2) the functional consequences of defective B7‐1 and B7‐2 signalling on primary and secondary T‐cell responses induced by LC and (3) the mechanism by which UVBR interferes with B7‐1 and B7‐2 expression. Ultraviolet‐B radiation dose‐dependently inhibited the culture‐induced upregulation of B7‐1 and B7‐2 on LC from both UVB‐susceptible (UVBs, C57BL/6) and UVB‐resistant (UVBR, Balb/c) mice and abrogated their capacity to stimulate proliferation of naive alloreactive T cells and of the KLH (keyhole limpet hemocyanin)‐specific T helper (Th)1 clone HDK‐1. The UVBR‐induced suppression of B7‐1 and B7‐2 on LC and their perturbed APC function were related, because exogenous triggering of the B7/CD28 pathway with a stimulatory monoclonal antibody (mAb) for CD28 to UVB‐irradiated LC partially restored T‐cell proliferation. Such reconstitution was not observed when the mAb was added to killed LC, indicating that the UVBR‐induced suppression of APC function was not due to lethal effects on LC. Conditioned supernatants from UVB‐irradiated epidermal cells did not inhibit the functional upregulation of B7‐1 and B7‐2, suggesting that UVBR inhibits B7‐1 and B7‐2 upregulation by acting directly on LC and not by altering LC costimulatory function via release of soluble immunosuppressive factors. In conclusion, UVBR distorts the functional expression of B7‐1 and B7‐2 on LC from both UVBs and UVBR mice, thereby contributing to the failure of UVB‐irradiated LC to stimulate resting alloreactive T cells or KLH‐specific Thl cells.
Experimental Dermatology | 1995
Jan C. Simon; Henning C. Dittmar; Erwin Schöpf; Jörg Wilting; Bodo Christ; Roland de Roche
Abstract Detailed studies on the biology of Langerhans cells (LC), which account for only 1‐3% of all epidermal cells, require isolation from their cutaneous symbionts. Several techniques of LC isolation have been reported, including positive enrichment with mAb coupled to immuno‐magnetic beads. The disadvantage of this technique is the size of the beads (= 2‐5 μm), which can interfere with subsequent phenotypic and functional analyses. This limitation prompted us to test wheter paramagnetic microbeads (15 nm) employed by the MACS™ system could be used to purify LC from human skin. To isolate fresh LC (fLC), epidermal cell suspensions (EC) were stained with anti‐CD la mAb and with appropriate secondary reagents conjugated to microbeads and to FITC. They were then passed over a separation column and exposed to a strong magnetic field. Thereafter both CD la‐depleted and CD la‐enriched cells were collected. Cultured LC (cLC) were isolated by staining 72‐h cultured EC with anti‐HLA‐DR mAb followed by the same isolation procedure. Using this technique, we could routinely isolate viable EC that were 45‐88% CD la or HLA‐DR+ as determined by FACS. Two‐color FACS analysis demonstrated the majority of MACS‐purified cells to be CDla+/HLA‐DR+, indicating that they were indeed LC. By transmission electron microscopy (TEM), the MACS‐purified CDla+/HLA‐DR+ cells showed typical ultrastructural characteristics of LC. Furthermore, MACS‐purified fLC or cLC were functionally intact, because they stimulated the proliferation of alloreactive T cells in a primary, one‐way, mixed epidermal cell leukocyte reaction (MECLR). We conclude that MACS‐separation is an efficient and rapid method to isolate human fLC and cLC of high purity and unimpaired function.
Photochemistry and Photobiology | 1998
Lone Skov; Henrik Hansen; Henning C. Dittmar; Jonathan Barker; Jan C. Simon; Ole Baadsgaard
Sensitization on skin exposed to acute low‐dose UVB irradiation separates normal humans into two phenotypically distinct groups: One group, following sensitization on UVB‐irradiated skin, develops contact sensitivity, designated UVB resistant (UVB‐R) and the second group, following sensitization on UVB‐irradiated skin, fails to develop contact sensitivity, designated UVB susceptible (UVB‐S). To investigate whether UVB susceptibility in humans is related to antigen‐presenting activity in the skin we studied the effect of UVB irradiation on the number and function of the epidermal antigen‐presenting cells in volunteers identified as UVB‐R and UVB‐S. Single cell suspensions of epidermal cells from control skin and skin exposed to 3 minimal erythema doses (MED) of UVB 3 days previously were stained for Langerhans cells (CD1a+HLA‐DR+) and epidermal macrophages (CD1a‐HLA‐DR+). The UVB exposure of the skin significantly decreased the percentage of Langerhans cells (UVB‐R: n = 7, P < 0.02, UVB‐S: n = 6, P < 0.03) and increased the percentage of epidermal macrophages (UVB‐R: n = 7, P < 0.03, UVB‐S: n = 6, P < 0.03) however to the same degree in both the UVBR and the UVB‐S group. To study the effect on Langerhans cell alloreactivity, epidermal cells were harvested immediately after UVB irradiation. However, in both UVB‐R and UVB‐S subjects the Langerhans cell alloreactivity was blocked to the same degree immediately after UVB irradiation compared to nonirradiated epidermal cells. To determine the effect of UVB irradiation on epidermal macrophages, epidermal cells were harvested 3 days after UVB irradiation. Irradiated epidermal cells from both UVB‐R and UVB‐S subjects demonstrated a strong antigen‐presenting capacity compared to epidermal cells from control skin leading to activation of T cells that mainly secrete interferon (1FN)‐γ and not interleukin (IL)‐4. In conclusion we found that UVB susceptibility was not correlated with the number of Langerhans cells or epidermal macrophages in the skin at the same time of sensitization. Neither was it correlated with the capacity of Langerhans cells nor UVB‐induced epidermal macrophages to activate T cells in vitro.
Immunotechnology | 1998
Christian Termeer; Johannes M. Weiss; Henning C. Dittmar; Wolfgang Vanscheidt; Erwin Schöpf; Jan C. Simon
Here we report the quantification of T cell adhesion to endothelial cells using the luminescence marker BioLite. A new application for this substance was established using a microassay for the detection of TK-1 mouse T-lymphoma cell adhesion to unstimulated or TNF alpha-stimulated eEnd.2 mouse vascular endothelioma cells. Prelabelling of TK-1 with the marker resulted in luminescence values linearly related to the number of adherent T cells. The marker was not toxic for T cells or endothelial cells nor did it interfere with the expression or function of adhesion molecules on T cells (LFA-1, VLA-4) or endothelial cells (ICAM-1, VCAM-1). When compared with established techniques to quantify T cell/endothelial cell adhesion, i.e. microscopical evaluation or isotope prelabelling of T cells, this method was found to be just as reliable and sensitive.
Journal of Dermatological Science | 1998
Henning C. Dittmar; Johannes M. Weiss; Christian Termeer; Ralf W. Denfeld; M.B. Wanner; Jan C. Simon
Ultraviolet B (UVB, 290-320 nm) radiation is known to suppress the immune function of epidermal Langerhans cells. We have recently described that in vitro UVB irradiation perturbs the antigen-presenting cell function of Langerhans cells by inhibiting their expression of functional B7 costimulatory molecules (B7-1, B7-2). The aim of this study was to determine wavelength-specific UV effects on Langerhans cells function in vivo, specifically UVB and UVA-1. To address this issue, volunteers were irradiated on the sun protected volar aspects of their forearms with 3 x minimal erythema dose of UVB (Philips TL-12) and UVA-1 (UVASUN 5000 Mutzhaas). Langerhans cells were isolated from suction blister roofs immediately following irradiation. Langerhans cells isolated from UVB- but not from UVA-1-irradiated skin failed to activate naïve resting allogeneic T cells (mixed epidermal cell leukocyte reaction) or primed tetanus toxoid reactive autologous T cells. Langerhans cells isolated from sham-irradiated or UVA-1-irradiated skin strongly upregulated B7-2 molecules during short-term tissue culture. By contrast, Langerhans cells from UVB-irradiated skin did not upregulate B7-2 molecules. Furthermore, exogenous stimulation of the B7 pathway by anti-CD28 stimulatory monoclonal antibodies restored the capacity of UVB-irradiated Langerhans cells to activate both alloreactive and tetanus toxoid-reactive T cells, implying suppressed antigen-presenting cell activities and perturbed B7 expression of Langerhans cells isolated from UVB-irradiated skin are related. Those studies demonstrate that in vivo UVB, but not UVA-1, interferes with the activation-dependent upregulation of B7 molecules on Langerhans cells, which in turn is of functional relevance for the perturbed antigen-presenting cell function of Langerhans cells within UVB- but not UVA-1-irradiated skin.
Journal of Cell Biology | 1997
Johannes M. Weiss; Jonathan P. Sleeman; Andreas C. Renkl; Henning C. Dittmar; Christian Termeer; Sabine Taxis; Norma Howells; Martin Hofmann; Gabriele Köhler; Erwin Schöpf; Helmut Ponta; Peter Herrlich; Jan C. Simon
Journal of Investigative Dermatology | 2000
Christoph M. Schempp; Henning C. Dittmar; Daniela Hummler; Birgit Simon-Haarhaus; Erwin Schöpf; Jan C. Simon; Jürgen Schulte-Mönting
Journal of Investigative Dermatology | 1999
Henning C. Dittmar; Johannes M. Weiss; Christian Termeer; Ralf W. Denfeld; Erwin Schöpf; Jan C. Simon; Marcus B. Wanner; Lone Skov; Jonathan W.N. Barker; Ole Baadsgaard