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T Bieber

Publications and source records attributed to T Bieber.

At least 109 records · Page 6Linked to original sources
PubMed1997

A short-term trial of tacrolimus ointment for atopic dermatitis. European Tacrolimus Multicenter Atopic Dermatitis Study Group.

BACKGROUND: Tacrolimus (FK 506) is an effective immunosuppressant drug for the prevention of rejection after organ transplantation, and preliminary studies suggest that topical application of tacrolimus is effective in the treatment of atopic dermatitis. METHODS: We conducted a randomized, doubleblind, multicenter study that compared 0.03 percent, 0.1 percent, and 0.3 percent tacrolimus ointment with vehicle alone in patients with moderate to severe atopic dermatitis. The ointment was applied twice daily to a defined, symptomatic area of 200 to 1000 cm2 of skin for three weeks. The primary end point was the change in the summary score for erythema, edema, and pruritus between the first and last days of treatment. RESULTS: After three weeks of treatment, the median percentage decrease in the summary score for dermatitis on the trunk and extremities was 66.7 percent for the 54 patients receiving 0.03 percent tacrolimus, 83.3 percent for the 54 patients receiving 0.1 percent tacrolimus, 75.0 percent for the 51 patients receiving 0.3 percent tacrolimus, and 22.5 percent for the 54 patients receiving vehicle alone (P<0.001). The results for the face and neck were similar. The differences among the three tacrolimus groups were not statistically significant. A sensation of burning at the site of application was the only adverse event that was significantly more frequent with tacrolimus than with vehicle alone (P<0.001). Throughout the study, most patients in all three tacrolimus groups had blood concentrations of tacrolimus below 0.25 ng per milliliter. The highest concentration was 4.9 ng per milliliter, which was reported in the group receiving 0.3 percent tacrolimus. CONCLUSIONS: The short-term application of tacrolimus ointment is effective in the treatment of atopic dermatitis, with the sensation of burning being the main side effect.

Administration, Cutaneous↗
PubMed1997

Functions of Fc receptors on human dendritic Langerhans cells.

Immature dendritic cells are antigen presenting cells highly specialized for capturing and processing foreign protein antigens. These cells express Fc gamma RII and Fc epsilon RI which, by their ability to internalize and use the endocytic pathway, increase their capacity to process antigens. Immature dendritic cells, such as epidermal Langerhans cells, also release soluble forms of Fc gamma RII. These latter molecules are likely to compete with the membrane-associated Fc gamma R to diminish or abrogate the capacity of dendritic cells to present immune complexes, as suggested by our in vitro experiments using both human and mouse epidermal Langerhans cells. However, when dendritic cells mature in vitro and become efficient stimulators of resting T cells, they rapidly down-regulate and sometimes completely abolish the expression of their membrane-associated Fc gamma R and Fc epsilon RI. Consequently, they lose or at least strongly diminish their capacity to capture immune complexes. At this stage, the release of soluble Fc gamma R by dendritic cells is also markedly diminished. One can hypothesize that the membrane-associated Fc gamma RII and the soluble Fc gamma RII are molecules expressed when dendritic cells are potent capturing and processing cells, the soluble Fc gamma RII molecule acting by competition as a negative regulatory element on the Fc gamma RII-mediated internalization of IgG-containing immune complexes. Thus, the expression of membrane-associated Fc gamma R and Fc epsilon RI, as well as the release of soluble Fc gamma R, would seem to characterize the immature stage of dendritic cells.

Humans↗
PubMed1997

Leprosy type 1 reaction as the first manifestation of borderline lepromatous leprosy in a young native German.

While leprosy is usually a chronic disease, leprosy reactions may lead to acute problems. These reactions most often occur after initiation of therapy, but can also develop before treatment. Leprosy rarely presents with a reaction. We describe a German patient who presented in this unusual way in order to demonstrate the various tools used to confirm the diagnosis. A young German woman suddenly developed progressive functional loss of the left hand and within a few weeks an increasing number of erythematous macules and nodules appeared. Histological examination of a skin biopsy revealed tuberculoid granulomas, some located around small nerves; acid-fast bacilli were detected microscopically and DNA from Mycobacterium leprae was identified by polymerase chain reaction in the biopsy and a nasal swab; serological tests were positive. The disease was classified as borderline lepromatous leprosy. The acute neuritis followed by skin lesions represented a leprosy type 1 reaction in which the immune system reacts to bacilli previously unrecognized in nerve tissue, both in nerve and skin.

Acute Disease↗
PubMed1996

New insights in the structure and biology of the high affinity receptor for IgE (Fc epsilon RI) on human epidermal Langerhans cells.

The recent structural and functional analysis of the high affinity receptor for IgE (Fc epsilon RI) expressed on human epidermal Langerhans cells (LC) revealed new aspects of the biology of this structure. In contrast to basophils and mast cells where this receptor seems to be expressed constitutively at a constant level, the expression of Fc epsilon RI on LC varies on the donor and the inflammatory environment of the cells and lacks the classical beta-chain. This also implies functional differences most probably related to the expression level. Although the signalling pathway seems to be similar to that of basophils or mast cells, LC from individuals with atopic dermatitis are fully activated by receptor ligation while LC from normal individuals fail to exhibit calcium mobilization under the same conditions. Finally, LC from normal and atopic individuals use Fc epsilon RI to maximize antigen uptake via specific IgE and subsequent presentation to T cells. Thus, Fc epsilon RI expressed on LC differs in terms of structure and function from that expressed on effector cells of anaphylaxis.

Antigen Presentation↗
PubMed1996

Fc epsilon RI on antigen-presenting cells.

The high-affinity receptor for IgE, Fc epsilon RI, expressed on antigen-presenting cells such as monocytes and Langerhans' cells exhibits profound differences to its homologue expressed on mast cells and basophils. The lack of the beta chain, the presence of an intracellular pool of preformed alpha chains, highly variable surface expression, and its function (to provide antigen focusing for T cells) are some of the main issues which have led us to consider the functional role of this receptor in a new light.

Antigen-Presenting Cells↗
PubMed1996

Immunomorphological and ultrastructural characterization of Langerhans cells and a novel, inflammatory dendritic epidermal cell (IDEC) population in lesional skin of atopic eczema.

We investigated epidermal cell suspensions prepared from lesional and nonlesional atopic eczema skin, other inflammatory skin conditions, and normal human skin for high-affinity IgE receptor (Fc epsilon RI) expression on dendritic CD1a cells by quantitative flow cytometric analysis. A single CD1a bright/CD1b neg/Fc epsilon RI dim/CD23 neg/CD32 dim/HLA-DR bright/CD36 neg population was found in normal skin. In contrast, lesional skin of atopic eczema and other inflammatory skin diseases harbored variable proportions of two distinct CD1a populations. Both populations exhibited typical ultrastructural features of Langerhans cells, but the second one lacked Birbeck granules and was unreactive to the Birbeck granule-specific LAG antibody. Both populations differed phenotypically: classical Langerhans cells were CD1a bright/CD1b neg/Fc epsilon RI dim/CD23 neg/CD32 dim/HLA-DR bright/CD36 dim, while the second population was CD1a dim/CD1b dim/Fc epsilon RI bright/CD23 dim/CD32 dim/HLA-DR bright/CD36 bright. The highest Fc epsilon RI expression was found on the second CD1a population in lesional atopic eczema skin. Furthermore, Fc epsilon RI expression on CD1a cells correlated significantly with the serum IgE level of the patients. Thus, a distinct population of CD1a inflammatory dendritic epidermal cells different from classical Langerhans cells appears in the epidermis of lesional skin and is subjected to specific signals leading to the upregulation of Fc epsilon RI in atopic eczema skin.

Antigens, CD1↗
PubMed1996

Granulocyte/macrophage-colony-stimulating factor induces the migration of human epidermal Langerhans cells in vitro.

In the present study, we investigated the in vitro migratory activity of human epidermal Langerhans cells (LC). Freshly isolated LC exhibit very low spontaneous migration. In contrast, a strong migration is recorded 6 h after the isolation. This migration is due to the presence of GM-CSF released by surrounding keratinocytes in vitro. Picomolar concentrations of GM-CSF promote the migration of LC, but nanomolar concentrations are inhibitory. Checker-board experiments indicate that GM-CSF acts as a chemokinetic mediator for LC, Bulk cultured LC exhibit a significant decrease of their spontaneous migration but retain the capacity to respond to GM-CSF only at nanomolar concentrations. In contrast, LC cultured in the presence of picomolar concentrations of exogenous GM-CSF exhibit a spontaneous migratory activity comparable to that of 6 h rested LC but do not respond to GM-CSF. These results suggest that GM-CSF represents an essential factor triggering the egress of LC from their epidermal environment.

Cell Movement↗
PubMed1995

Activation of human epidermal Langerhans cells by engagement of the high affinity receptor for IgE, Fc epsilon RI.

Human epidermal Langerhans cells (LCs) bind IgE via the high affinity receptor (Fc epsilon RI), and therefore are suspected to be involved in the genesis of atopic diseases. In this study, we report that surface expression of Fc epsilon RI is increased dramatically on LCs from patients with atopic dermatitis (AD) when compared with nonatopic individuals. Cross-linking of Fc epsilon RI on LCs from nonatopic individuals and patients with AD leads to a rapid tyrosine phosphorylation of several proteins, including p72, p77, and p95. However, upon receptor ligation, calcium mobilization is only detected in LCs freshly isolated from patients with AD (responder LCs), but not in those from normal skin of healthy individuals (nonresponder LCs). The beta-chain of Fc epsilon RI is not detected in normal LCs and only in a minority of LCs from atopic individuals, indicating that it is not related to the capacity of LCs to respond to Fc epsilon RI-mediated activation. In contrast, LCs from both nonatopic and atopic individuals internalize Fc epsilon RI by receptor-mediated endocytosis as a prerequisite for Ag focusing. Therefore, LCs from normal individuals and individuals with AD differ functionally by their Fc epsilon RI expression and by a distinct ability to respond to Fc epsilon RI-mediated activation.

Antibodies, Monoclonal↗
PubMed1995

Membrane and soluble Fc gamma RII/III modulate the antigen-presenting capacity of murine dendritic epidermal Langerhans cells for IgG-complexed antigens.

Murine dendritic epidermal Langerhans cells (LC) are APC. This implies that LC take up, process, and present Ag to T cells. One way of doing so that could allow Ag internalization is provided by the low affinity receptors for the Fc region of IgG (Fc gamma R), which murine LC are known to express, although their isoform(s) and function(s) have not been defined. By using molecular biology and biochemical approaches, we demonstrated that LC expressed Fc gamma RIIb2 and Fc gamma RIII. Furthermore, LC internalized Fc gamma R by receptor-mediated endocytosis, as observed with gold-labeled anti-Fc gamma RII/III mAb or immune complexes. We demonstrated the biologic relevance of this process by observing that Fc gamma R-mediated Ag internalization improved by approximately 300-fold the Ag-presenting capacity of LC to T cells. Moreover, analysis of cell culture supernatants showed that two forms of soluble Fc gamma R (sFc gamma R) were released by LC: the first most probably was the secreted transmembrane-deleted Fc gamma RII isoform, Fc gamma RIIb3, and the second was a soluble receptor probably derived from the membrane-associated Fc gamma RII/III. The ability of two recombinant forms, corresponding to the two sFc gamma R released by LC, to inhibit Fc gamma R-mediated presentation enhancement was assayed. Preincubation of IgG-complexed Ag with either rsFc gamma R led to a dose-dependent decrease in the Ag-presenting capacity of LC. Taken together, our results suggest that, in vivo, LC express membrane Fc gamma R, which increase their Ag-presenting capacity for IgG-complexed Ag, and release sFc gamma R, which might be able to modulate this Ag presentation.

Animals↗
PubMed1995

Characterization of the protein tyrosine phosphatase CD45 on human epidermal Langerhans cells.

Human Langerhans cells (LC) express CD45, but clear data about the isoform(s) and their function(s) are lacking. In the present study, double labeling experiments reveal that freshly isolated LC from normal skin are CD45RO+/RA-/RB-. However, after isolation and short-time culture where LC undergo an in vitro maturation resembling that to lymphoid dendritic cells, CD45RB emerges whereas CD45RO expression decreases. This evolution results from dynamic alternative RNA splicing. Addition of granulocyte-macrophage colony-stimulating factor or tumor necrosis factor-alpha to short-time cultures has no significant effect on CD45RB, but both cytokines accelerate the loss of CD45RO. LC isolated from lesional skin of atopic eczema highly express CD45RO and CD45RB. Cross-linking of CD45 on LC isolated from atopic individuals inhibits the calcium mobilization in response to activation via Fc epsilon receptor type I (Fc epsilon RI). Hence, the protein tyrosine phosphatase CD45 from human LC is subjected to a splicing phenomenon related to the differentiation and activation stage of these cells and regulates their Fc epsilon RI-mediated activation.

Calcium↗
PubMed1995

[Role of Langerhans cells in the physiopathology of atopic dermatitis].

The demonstration of IgE receptors on the surface of epidermal dendritic cells and on other antigen presenting cells is a crucial element in the understanding of the pathophysiological role of these cells in the genesis of atopic disease, and especially the atopic dermatitis (AD). The sensibilisation phase to an aeroallergen at the level of nasal or bronchial mucosa and even at the skin may be mediated by dendritic cells expressing Fc epsilon RI. Distinct forms of AD may then represent the equivalent of the ellicitation phase of the classical allergic contact dermatitis. Fc epsilon RI would lead, via specific IgE, to an efficient antigen capture, to the activation of the dendritic cells and finally to an antigen presentation. Thus, AD may represent the paradigma of an IgE-mediated type IV reaction.

Cytokines↗