Biomedical subjects

Stefan Beissert

Publications and source records attributed to Stefan Beissert.

26 records · Page 2Linked to original sources

PubMed2004

Neuropilin-1: a surface marker of regulatory T cells.

CD4+CD25+ regulatory T cells (Treg cells) control immune responsiveness to a large variety of antigens. The isolation and therapeutic manipulation of Treg cells requires the use of reliable surface receptors that are selectively up-regulated in Treg cells. On the basis of global gene expression studies, we identified neuropilin-1 (Nrp1) as a specific surface marker for CD4+CD25+ Treg cells. Nrp1, a receptor involved in axon guidance, angiogenesis, and the activation of T cells, is constitutively expressed on the surface of CD4+CD25+ Treg cells independently of their activation status. In contrast, Nrp1 expression is down-regulated in naive CD4+CD25- T cells after TCR stimulation. Furthermore, CD4+Nrp1(high) T cells express high levels of Foxp3 and suppress CD4+CD25- T cells. Thus, Nrp1 constitutes a useful surface marker to distinguish Treg cells from both naive and recently activated CD4+CD25+ non-regulatory T cells.

Animals↗

PubMed2003

Treatment of severe lichen planus with mycophenolate mofetil.

Lichen planus (LP) is an inflammatory skin disorder with a wide range of clinical appearances. The treatment of disseminated and especially erosive forms of LP is often difficult and disappointing. Activated T cells are important in the pathogenesis of LP as indicated by the dermal lymphocytic infiltrate leading to keratinocyte destruction and lesion formation. Similar histologic findings are present in graft-versus-host disease. Since T cells are key players in the development of both disorders and mycophenolate mofetil has been successfully introduced in the treatment of graft-versus-host disease, we have examined the therapeutic potential of this agent in 3 patients suffering from disseminated and erosive LP. Mycophenolate mofetil was well tolerated and induced complete remission in 2 patients, and substantial improvement in the third patient.

Adolescent↗

PubMed2003

Dendritic cells under investigation in autoimmune disease.

Autoimmune disorders play an increasing role in public health, especially in light of the fact of the growing aged population, which primarily develop such diseases. A clear understanding of the mechanisms leading to the development of autoimmune responses and finally to autoimmune disease does not exist. Autoimmunity is characterized by the presence of autoantibodies and/or autoreactive T cells and the corresponding organ manifestation. Following the discovery of autoreactive T cells found in the periphery of mice and humans, the old immunological concept that autoreactive T cells are completely deleted in the thymus during evolution has been revised in recent years. Although antigen-presenting cells and particularly dendritic cells are known to play an important role in the regulation of immune responses and the activation of T cells, recent evidence suggests that the role of dendritic cells in the development of autoimmunity has been underestimated previously. This article aims to give a general overview on the basic immunological principles involved and gives a short review of the current literature on the functional relevance of dendritic cells in various human and murine autoimmune disorders.

Animals↗

PubMed2003

Alterations in the vascular extracellular matrix of granulocyte macrophage colony-stimulating factor (GM-CSF) -deficient mice.

GM-CSF takes part in the cytokine network regulating the metabolism of extracellular matrix (ECM) during atherogenesis. Since data also point to an effect of GM-CSF on the vascular ECM in general, the vascular collagenous matrix was studied in wild-type and GM-CSF-deficient mice. Histological examination revealed a disorganized vascular ECM in GM-CSF-deficient mice involving the collagenous matrix and elastic fiber system. As shown by electron microscopy, collagen bundles were disrupted and reduced. The diameter of fibrils varied widely. mRNA expression of collagens and related molecules was studied. Fibrillar collagens were markedly reduced, alpha1(I)procollagen to 16.5% of control levels alpha1(III)procollagen was abolished whereas the expression level of network-forming alpha1(VIII)procollagen was not altered. As shown by in situ hybridization, the number of collagen-expressing cells was reduced. Matrix metalloproteinases and their inhibitor 1 were not affected by GM-CSF deficiency. Our studies demonstrate that GM-CSF plays a major role in the cytokine network regulating the metabolism of vascular collagens. GM-CSF deficiency leads to an altered composition of the vascular collagenous matrix, i.e., reduced amount of fibrillar collagen, altered ratio of fibrillar and network-forming collagen, and failures in the fibrillogenesis. We suggest that GM-CSF is a basic requirement for the maintenance of vessel wall integrity and resilience.

Animals↗

PubMed2003

Altered cutaneous immune parameters in transgenic mice overexpressing viral IL-10 in the epidermis.

IL-10 is a pleiotropic cytokine that inhibits several immune parameters, including Th1 cell-mediated immune responses, antigen presentation, and antigen-specific T cell proliferation. Recent data implicate IL-10 as a mediator of suppression of cell-mediated immunity induced by exposure to UVB radiation (280-320 nm). To investigate the effects of IL-10 on the cutaneous immune system, we engineered transgenic mice that overexpress viral IL-10 (vIL-10) in the epidermis. vIL-10 transgenic mice demonstrated a reduced number of I-A(+) epidermal and dermal cells and fewer I-A(+) hapten-bearing cells in regional lymph nodes after hapten painting of the skin. Reduced CD80 and CD86 expression by I-A(+) epidermal cells was also observed. vIL-10 transgenic mice demonstrated a smaller delayed-type hypersensitivity response to allogeneic cells upon challenge but had normal contact hypersensitivity to an epicutaneously applied hapten. Fresh epidermal cells from vIL-10 transgenic mice showed a decreased ability to stimulate allogeneic T cell proliferation, as did splenocytes. Additionally, chronic exposure of mice to UVB radiation led to the development of fewer skin tumors in vIL-10 mice than in WT controls, and vIL-10 transgenic mice had increased splenic NK cell activity against YAC-1targets. These findings support the concept that IL-10 is an important regulator of cutaneous immune function.

Animals↗

PubMed2002

Use of mutant mice in photoimmunological and photocarcinogenic investigations.

The mechanisms underlying UV-induced immunosuppression and the development of UV-induced skin cancer have been intensively investigated for decades. In particular, UV-induced DNA damage and UV-induced suppression of cellular immune responses were analyzed in great detail. During this time, several cellular and genetic pathways were identified, that are involved in photoimmunology and photocarcinogenesis. However, the direct effects of the complex UV-induced pathways on immunosuppression or on cutaneous tumor generation in vivo have not been able to be characterized with certainty so far. With the increasing availability of mutant mice that lack or overexpress certain genes, more information can be obtained with respect to the functional importance of individual gene products and the signaling pathways involved in UV-mediated immunomodulation and cancer development. This article is an overview of the results of UV-induced immunosuppression and photocarcinogenesis experiments obtained in different mutant mice.

Abatacept↗

PubMed2002

Role of immunomodulation in diseases responsive to phototherapy.

Within the last two decades phototherapy has turned out to be a major therapeutic strategy in dermatology and thus has significantly influenced the treatment of many dermatoses. The goals of therapeutic photomedicine are the suppression of ongoing disease processes and, more importantly, the prevention, modulation, or abrogation of pathogenic mechanisms causing the disease. Therapeutic photomedicine has been largely empirical and most of it is still empirical today. However, parts of it are already based on the advances in photoimmunology and molecular biology. Although, we are far from a detailed understanding of the mechanisms underlying phototherapy, there is increasing evidence that phototherapy acts via modulation of the immune system. Most of the effects of both ambient and therapeutic ultraviolet radiation are immunosuppressive in nature.

Animals↗

PubMed2002

Beta2 integrins are required for skin homing of primed T cells but not for priming naive T cells.

Beta2 integrins are of critical importance for leukocyte extravasation through vascular endothelia and for T cell activation. To elucidate the role of beta2 integrins in T cell-mediated immune responses, allergic contact dermatitis (ACD), irritant dermatitis, and delayed-type hypersensitivity (DTH) were assessed in mice lacking the beta2 integrin subunit, CD18. ACD and DTH responses, but not edema formation, were severely suppressed in CD18(-/-) mice. Extravasation of CD18(-/-) T cells into eczematous skin lesions was greatly impaired, whereas migration of Langerhans cell precursors and dendritic cells was normal in CD18(-/-) mice. CD18(-/-)lymph nodes (LNs) contained an abnormal population of CD3(-)CD44(high) lymphocytes and showed evidence of widespread T cell activation. T cells from regional LNs of sensitized CD18(-/-) mice proliferated in response to hapten challenge, and subcutaneous injection of sensitized syngeneic LN cells directly into ears of hapten-challenged naive recipients restored the defective ACD in CD18(-/-) mice, suggesting that CD18 is not required for priming of naive T cells but is indispensable for T cell extravasation. Thus, a dysfunction of T cells, in addition to granulocytes, may contribute to the pathophysiology of leukocyte adhesion deficiency type I, which arises from mutations in the human CD18 gene.

Animals↗