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G L Vejlsgaard

Publications and source records attributed to G L Vejlsgaard.

36 records · Page 2Linked to original sources
PubMed1992

T-cell receptor gamma delta-positive peripheral T-cell lymphomas presenting in the skin: a clinical, histological and immunophenotypic study.

Examination of biopsy samples from 62 patients with--or with suspected--cutaneous T-cell lymphoma (CTCL) revealed 2 cases in which the neoplastic cells were positive for the T-cell receptor (TCR) gamma delta complex. One patient had mycosis fungoides and 1 patient had a pleomorphic lymphoma of medium and large-cell type. Both cases showed aggressive courses with dissemination to internal organs and short survival times. The phenotypic examination showed that the neoplastic cells were positive with TCR delta 1, CD3, CD25, CD29, CD45R0 and CD54. No staining was seen with antibodies against framework determinants or variable regions on the TCR alpha beta heterodimer. Negative reactions were also seen with CD4, CD8, CD5, CD7, CD16, CD30 and CD57. It is concluded that rare CTCL express TCR gamma delta chains. These malignancies may originate from the TCR gamma delta-positive T cells seen in normal skin, and it is possible that their recognition may be important for clinical reasons.

Female↗
PubMed1991

Epidermal interleukin 1 alpha functional activity and interleukin 8 immunoreactivity are increased in patients with cutaneous T-cell lymphoma.

Previous studies have suggested that epidermal-derived interleukin-1 is involved in the pathogenesis of cutaneous T-cell lymphoma (CTCL); however, the findings are conflicting and studies that combine immunohistochemistry and functional activity have not been performed. We investigated the interleukin-1 level in epidermis of patients with cutaneous T-cell lymphoma using both immunohistochemistry, enzyme-linked immunosorbent assays, and the thymocyte co-stimulation assay. Using supernatants obtained from epidermal cell cultures, we found a significant but small increase of interleukin 1 alpha protein release from involved CTCL epidermis compared to normal epidermis from healthy individuals. Both keratinocytes and leukocytes could release interleukin-1 alpha, but the majority was derived from the keratinocytes. Interleukin-1 beta protein was not detectable. In the thymocyte assay, interleukin-1 alpha was found to be biologically active. When lymphokines derived from a T-cell clone obtained from involved CTCL skin were co-cultured with epidermal cells, an enhanced release of epidermal interleukin-1 alpha could be demonstrated. Because interleukin 1 alpha was increased, we investigated the presence of interleukin 1-inducible keratinocyte-derived interleukin 8 and found it increased in CTCL epidermis compared to normal epidermis from healthy individuals. This study demonstrated an elevated epidermal IL-1 alpha level and IL-8 immunoreactivity in CTCL epidermis, which suggests that this elevated level is induced by lymphokines released from activated T cells.

Cells, Cultured↗
PubMed1991

Expression of a cell adhesion protein (VLA beta) in normal and diseased skin.

Biopsies from normal skin (n = 17) and various cutaneous disorders (n = 83) were examined immunohistologically for reactivity with an antibody (CD29) against the common beta chain of the VLA integrin family. In normal skin, CD29 recognized a number of cell types, i.e. endothelial cells, fibroblasts, T lymphocytes and basal keratinocytes. Similar cells were positive in diseased skin, but the expression of VLA beta was upregulated on keratinocytes. The phenotype of the VLA beta-positive T cells was examined in more detail by staining with anti-T-cell antibodies, i.e. CD3, CD4, CD8, CD45RO (UCHL1) and CD45R (2H4). These studies showed that most of the T cells in normal skin, benign cutaneous conditions and early cutaneous T-cell lymphomas (CTCL) expressed a similar phenotype and resembled antigen committed 'memory' (helper/inducer) cells (CD4+, CD29+, CD45RO+, CD45R-). In advanced CTCL, expression of these antigens was more variable, and many of these infiltrates showed aberrant (or unusual) expression of CD29, CD45RO, CD45R and other T-cell antigens. It is concluded that several cells involved in cutaneous immune reactions express a molecule (VLA beta) which acts as a receptor for extracellular matrix components. This molecule is important for the attachment of cells to connective tissue constituents and may act to facilitate the migration of lymphocytes (and other cells) during immune reactions in normal and diseased cutaneous conditions. Advanced CTCL differ from the early lesions and it is possible that there is a progressive accumulation of increasingly malignant (or transformed) cells in these conditions.

Antigens, CD↗
PubMed1991

Use of antibodies against the variable regions of the T-cell receptor alpha/beta heterodimer for the study of cutaneous T-cell lymphomas.

Recent studies have suggested that antibodies against the variable (V) regions of the T-cell antigen receptor (TCR) may be used as markers for clonality and malignancy in T-cell infiltrates. We have investigated this by examining biopsy samples from 45 patients with cutaneous T-cell lymphomas (CTCL) for reactivity with seven antibodies against different V-gene families on the TCR alpha/beta heterodimer, i.e. ICI (V beta 5a), W112 (V beta 5b), OT145 (V beta 6a), 16G8 (V beta 8a), S511 (V beta 12a), F1 (V alpha 2a) and LC4 (alpha beta Va). Serial biopsies were available in 13 patients and a total of 62 samples were studied. The neoplastic cells in five cases were positive for either V beta 5 (one case), V beta 6 (one case), V beta 8 (two cases) or V beta 12 (one case). In the remaining 40 cases, no staining was seen of the neoplastic cells. These findings indicate that while antibodies against the TCR V-regions may be used as clonotypic markers for certain T-cell neoplasms, there is as yet not a sufficient number of anti-TCR V-region antibodies available for the routine diagnosis of these conditions.

Antibodies, Monoclonal↗
PubMed1991

Expression of intercellular adhesion molecule-1 (ICAM-1) in benign naevi and malignant melanomas.

Intercellular adhesion molecule-1 (ICAM-1) is a membrane-bound glycoprotein that is a ligand for lymphocyte function-associated antigen-1 (LFA-1) and is important for a number of cell adhesions in immune reactions. The molecule is expressed by several cell types (e.g. macrophages, endothelial cells, keratinocytes, melanoma cells and cell lines) and there are some indications that expression of this molecule in melanocytic lesions is confined to malignant tumours and is more pronounced in metastatic and advanced tumours than in earlier lesions. In an attempt to elucidate this issue, we have studied biopsy samples from benign naevi (n = 7) and malignant melanomas (n = 33) regarding reactivity with monoclonal anti-ICAM-1 (CD54). The results indicate that the great majority of malignant melanomas are ICAM-1-positive. The most abundant staining is seen in metastatic melanomas. In primary melanomas, staining is more variable and generally weaker. However, no correlation was found between the degree of ICAM-1 labelling and the degree of tumour invasion. Furthermore, ICAM-1 expression was not confined to malignant lesions, but was also seen in benign naevi. These data contrast with earlier reports and indicate that ICAM-1 expression is unlikely to be of major prognostic or diagnostic value in melanocytic tumours.

Antigens, CD↗
PubMed1990

Malignant lymphomas of true histiocytic origin. A clinical, histological, immunophenotypic and genotypic study.

The clinical, histological, immunophenotypic and genotypic properties of four cases of lymphoma of true histiocytic origin are described. The cases were identified by typing 925 non-Hodgkin's lymphomas by immunophenotypic and/or genotypic techniques, and they all presented with skin lesions. The histological and immunophenotypic examination showed dense, diffuse infiltrates of markedly pleomorphic mononuclear cells that were positive for macrophage-associated markers, and negative for B-cell, T-cell and myeloid cell-associated antigens. Staining for Ki-1 and epithelial membrane antigen was also negative. Gene rearrangements studies were performed in three cases, and all of these showed germline configuration of both T-cell receptor and immunoglobulin genes. In all cases, the clinical course was aggressive with rapid and widespread dissemination to internal organs, poor response to conventional chemotherapy, and short survival times (0.5 to 14 months). This suggests that although true histiocytic tumours are very rare, their recognition may be important for clinical and/or prognostic reasons.

Adult↗
PubMed1990

T cell receptor beta-chain gene rearrangement without gamma-chain gene rearrangement in cutaneous T cell lymphoma: an unusual finding.

T cells from the blood and skin of a patient with cutaneous T cell lymphoma demonstrated rearrangement of the T cell receptor beta-chain gene in the absence of rearrangement of the gamma-chain gene. To our knowledge, this has not been previously reported. This finding was unexpected in light of prevailing concepts of T cell ontogeny. Potential explanations for it are discussed.

Aged↗
PubMed1990

Autoantibodies to lamins A and C in sera of patients showing peripheral fluorescent antinuclear antibody pattern on HEP-2 cells.

Lamins A, B, and C are the major proteins of a polymeric structure called nuclear lamina, which is intercalated between chromatin and the inner membrane of the nuclear envelope. Using immunofluorescence on HEp-2 cells, specific enzyme-linked immunosorbent assay, and Western blotting performed against nuclear lamina preparation from Ehrlich ascites tumor cells, we characterized three patients, whose sera contained antibodies to nuclear lamins. The reaction pattern observed in two of the patients may result from single or combined occurrence of anti-lamin A and C antibodies. The third patient had antibodies that probably recognized an epitope in the carboxy-terminal region of lamin C. The sera were donated by a heterogeneous group of patients, and no common clinical or laboratory signs seemed to link them together.

Adult↗
PubMed1990

Genotypic analysis of T-cell clones derived from cutaneous T-cell lymphoma lesions demonstrates selective growth of tumor-infiltrating lymphocytes.

The nature of T cells contained within cutaneous lesions of cutaneous T-cell lymphoma (CTCL) has not been studied at the clonal level. T cells extracted from skin lesions of two CTCL patients were cloned by limiting dilution and propagated in interleukin-2 (IL-2) containing medium with periodic lectin stimulation. Twelve T-cell clones were derived from each patient. In both cases, genotypic analysis of the T-cell clones revealed that these clones had T-cell receptor (TCR) beta- and gamma-chain gene rearrangements distinct from the predominant, presumably malignant, clone present in the skin, lymph nodes, or blood. This suggests that they were derived from presumably reactive (non-malignant) T cells. Furthermore, these clones had gene rearrangements different from each other, indicating their multiple clonal origins. The failure to propagate in vitro the CTCL T-cell clone suggests that CTCL cells may have growth requirements different from normal T cells. Thus, conventional T-cell culturing methods using IL-2 and lectins as mitogen may selectively propagate the presumably reactive T cells contained within the skin lesions. The ability to selectively grow these reactive lesional T cells (so-called tumor infiltrating lymphocytes) raises the possibility that these cells could be used in adoptive immunotherapy.

Cell Division↗
PubMed1990

Cutaneous T-cell lymphoma lesional epidermal cells activate autologous CD4+ T lymphocytes: involvement of both CD1+OKM5+ and CD1+OKM5- antigen-presenting cells.

Cutaneous T-cell lymphoma is characterized by infiltration of the skin by activated CD4+ T lymphocytes. The mechanism by which these T lymphocytes achieve and maintain their activated state is unknown. Antigen-specific activation of T lymphocytes is dependent upon antigen-presenting cells which express HLA-DR class II major histocompatibility complex molecules, such as epidermal Langerhans cells. In addition to CD1+DR+ Langerhans cells, cutaneous T-cell lymphoma lesional epidermis contains major histocompatibility complex class II positive non-Langerhans cell populations, including CD1+OKM5+ bone-marrow-derived cells and DR+ keratinocytes. We asked whether any of these epidermal cell populations demonstrate capacity to activate T lymphocytes. Various numbers of epidermal cells from uninvolved and involved cutaneous T-cell lymphoma plaques were therefore used to stimulate autologous CD4+ and CD8+ T lymphocytes in the absence of exogenous antigen. Involved epidermal cells potently induced proliferation of CD4+ T lymphocytes (S.I. +/- SEM = 466 +/- 45). In contrast, uninvolved epidermal cells only induced background levels of proliferation (S.I. +/- SEM = 2 +/- 0.5, N = 8, p less than 0.01). Neither involved nor uninvolved epidermal cells were able directly to activate CD8+ lymphocytes. The capability of involved epidermal cells to activate CD4+ T lymphocytes was dependent upon CD1+DR+ leukocytes and not DR+ keratinocytes, because depletion of either HLA-DR+, CD1+ or HLe1+ epidermal cells totally abrogated the T-lymphocyte proliferation. Interestingly, on a cell per cell basis CD1+DR+ cells obtained from involved skin, demonstrated relative to CD1+DR+ cells from uninvolved skin, enhanced capacity to activate CD4+ T lymphocytes. Furthermore, CD1+OKM5+ cells from involved epidermis stimulated autologous CD4+ T lymphocytes. This indicates that a unique hitherto undescribed CD1+OKM5+ epidermal antigen-presenting cell population may participate in T-lymphocyte activation. These findings provide support for the concept that the epidermal cells in cutaneous T-cell lymphoma patients, particularly the antigen-presenting cells, may contribute significantly to the activation of CD4+ malignant and/or non-malignant inflammatory T lymphocytes within the skin.

Antigen-Presenting Cells↗
PubMed1990

Keratinocyte and epidermal leukocyte expression of CD36 (OKM5) in benign and malignant skin diseases.

CD36 recognizes a 88 Kd glycoprotein, found on different cell populations involved in immunoregulation and are induced on keratinocytes by in vitro treatment with gamma-interferon. Therefore, we obtained skin biopsies from 48 patients with various dermatological diseases and from 5 healthy volunteers and stained these with monoclonal antibodies OKM5 (CD36), anti-HLA-DR and OKT6 (CD1a) using a three stage immunoperoxidase method. In normal skin, CD36 expression was not observed. In contrast, keratinocytes in diseased skin were CD36+. In most cases, the staining was restricted to the stratum granulosum and the stratum spinosum, but in psoriasis, squamous cell carcinoma and lymphomatoid papulosis, more extensive staining of keratinocytes was seen. In addition, CD36+ epidermal leukocytes were found in allergic patch-test infiltrates and in mycosis fungoides. The findings of CD36 expression by epidermal cells within a broad spectrum of dermatological diseases indicate a role for these cells in the regulation of immune reactions in the skin.

Antibodies, Monoclonal↗
PubMed1990

Abnormal function of CD4+ helper/inducer T lymphocytes in a patient with widespread human papillomavirus type 3-related infection.

Human papillomavirus-induced infections may be associated with cellular immunodeficiency. However, very little is known about the dysfunctional interactions among T lymphocytes, B lymphocytes, and antigen-presenting cells. A 30-year-old heterosexual man with a 10-year history of persistent multiple refractory flat wart lesions containing human papillomavirus type 3-related DNA sequence was studied. The patient had a severe depletion of CD4+ T lymphocytes and a compensatory increase in the number of CD8+ T lymphocytes. Impaired T-lymphocyte response to various stimuli was found. Depletion of the increased number of CD8+ T lymphocytes, which suppressed immunoglobulin production in vitro, did not restore the impaired T-lymphocyte response. Immobilized anti-CD3 beads that stimulate the T lymphocyte antigen complex in the absence of antigen-presenting cells indicated a T-lymphocyte defect, rather than a decreased antigen-presenting cell function. Thus, the pronounced cellular immunodeficiency was due to abnormal function of the CD4+ helper/inducer T lymphocytes.

Adult↗
PubMed1989

Kinetics and characterization of intercellular adhesion molecule-1 (ICAM-1) expression on keratinocytes in various inflammatory skin lesions and malignant cutaneous lymphomas.

The kinetics of expression of the intercellular adhesion molecule-1 (ICAM-1) were studied on keratinocytes in skin biopsy specimens of sensitive persons in whom the haptens were applied in a standardized format for allergic contact dermatitis testing. There was no ICAM-1 expressed on keratinocytes of normal skin; ICAM-1 was induced as early as 4 hours after the application of the patch in some subjects. By 48 hours after the application of the patch, all specimens contained ICAM-1-positive keratinocytes. This was concurrent with a heavy mononuclear cell dermal infiltrate and maximum clinical manifestations. Expression of human lymphocyte antigen (HLA)-DR or other inducible surface proteins on keratinocytes under these conditions was much less frequent. When specimens from primary irritant dermatitis were used, only 1 of 14 cases had keratinocytes expressing ICAM-1 at 48 hours, the time of maximum clinical manifestation. Among benign inflammatory lesions, most cases resembled the allergic patch test specimens in that ICAM-1 was expressed to a large degree on keratinocytes. Again, the expression of HLA-DR was variable. Malignant skin lesions, on the other hand, were much less consistent and generally lower in terms of ICAM-1 expression on keratinocytes. Furthermore, in contrast to the benign cutaneous conditions, some malignant skin lesions contained keratinocytes that expressed class II antigens or other inducible surface proteins in the absence of ICAM-1. These data suggest that ICAM-1 plays a role in the specific immune response by facilitating either antigen presentation or lymphocytic infiltration.

Adult↗
PubMed1989

Decreased number and function of antigen-presenting cells in the skin following application of irritant agents: relevance for skin cancer?

The mechanism of irritant dermatitis and the immunologic consequences of such reactions are unclear. We evaluated the number and function of epidermal antigen-presenting cells contained in epidermal cell suspensions obtained from normal and irritant patch test reaction sites. Application of sodium lauryl sulfate or croton oil to human skin in vivo resulted in a progressive depletion in the number of epidermal OKT6+HLA-DR+ (T6+DR+) Langerhans cells (LC) from 3.1 +/- 0.2% of total epidermal cells (EC) to 1.2 +/- 0.1% after 8 d (mean values +/- SEM, N = 9). Between 1-4 d irritant patch test sites demonstrated an influx of non-Langerhans cell T6-DR+ cells. These cells were not DR+ keratinocytes but appeared to be of bone marrow derivation because they expressed the marker, HLe1. Among bone marrow derived cells, the T6-DR+EC appeared to be of monocyte, macrophage lineage, because they expressed the determinant recognized by the OKM5 (M5) antibody. Despite the induction of M5+DR+EC the total number of DR+EC showed progressively decreasing percentages over an 8-d period. Partial recovery to 73 +/- 12% of control value was observed at 2 weeks, with full recovery by 4 weeks after challenge. Concomitantly with the depletion of DR+EC, the capacity of EC to present alloantigens to T cells decreased. This reduction in antigen-presenting cell activity was strongly correlated to the reduction in total DR+ EC (r = 0.94, p less than 0.05). Thus, the capacity of irritants such as croton oil to abrogate the function of epidermal antigen-presenting cells may be related to the tumor promoting potential of these agents.

Administration, Cutaneous↗
PubMed1989

Intercellular adhesion molecule-I (ICAM-I) expression correlated to inflammation.

The presence of intercellular adhesion molecule-I (ICAM-I) on keratinocytes of psoriatic skin lesions before and during 8-methoxapsoralen and UVA light (PUVA) treatment was studied. ICAM-I was expressed on the keratinocytes in biopsies of the skin lesions of five patients with psoriasis. The patients who responded to PUVA treatment had a concurrent reduction of ICAM-I expression on the keratinocytes with a reduction of the number of cells in the mononuclear cellular infiltrate and a lessening of the severity of the disease. Patients who went into remission during therapy and then relapsed showed an increase in ICAM-I expression on keratinocytes with an increase in the number of cells in the mononuclear cell infiltrate and an increase in the severity of the disease. HLA-DR expression on keratinocytes was variable during treatment and showed no strong correlation with disease severity.

Antigens, Surface↗