Expression of intercellular adhesion molecule-1 on the vascular endothelium in nasal polyps before, during and after topical glucocorticoid treatment.

Nasal polyposis is a result of a chronic inflammatory disorder in the upper airways. In vitro studies have revealed that extravasation of leucocytes requires interactions between several sets of adhesion molecules expressed on the circulating leucocytes and the vascular endothelium. Therefore, the endothelial expression of intercellular adhesion molecule-1 (ICAM-1) in biopsies from polyps and inferior turbinates was investigated by the use of immunohistochemical staining. Biopsies were obtained from 11 patients suffering from nasal polyposis before, during and after treatment with 100 microg budesonide (Rhinocort Turbuhaler) in each nostril twice daily. Before, during and after treatment, ICAM-1 was expressed in the majority of vessels in polyps and mucosa of inferior turbinates. The intensity of endothelial ICAM-1 expression in polyps was significantly reduced during topical glucocorticoid treatment compared with the pretreatment and posttreatment levels (p < 0.005). In biopsies from the inferior turbinates, the intensity of the endothelial ICAM-1 expression was lower during treatment than after discontinuation of medical treatment (p < 0.005). In conclusion, topical budesonide treatment seems to downregulate ICAM-1 expression on the vascular endothelium in nasal polyps. Such an effect may interfere with leucocyte extravasation and partially account for the anti-inflammatory effect of local glucocorticoid treatment in human nasal polyposis.

Antigen-presenting activity of non-Langerhans epidermal cells in contact hypersensitivity reactions.

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.

UM4D4+ (CDw60) T cells are compartmentalized into psoriatic skin and release lymphokines that induce a keratinocyte phenotype expressed in psoriatic lesions.

UM4D4 (CDw60), the surface molecule of a novel antigen-independent T-cell activation pathway, was found to be highly expressed on lesional psoriatic T cells. To examine whether UM4D4 represents a T-cell activation pathway for psoriatic T cells, a T-cell line was initiated from an acute skin lesion and cloned by limiting dilution. Clonality was verified by analysis of T-cell receptor gene rearrangement. All T-cell clones tested, whether CD4+2H4+CD8-, CD4+2H4-CD8-, or CD4-CD8+CD11b-, expressed UM4D4 and were activated by the monoclonal antibody anti-UM4D4. Lesional psoriatic T-cell clones were heterogeneous in the degree of anti-UM4D4-induced proliferation and in their production of IL-2 and gamma-interferon. Lymphokines released by anti-UM4D4 activation were capable of inducing ICAM-1 and HLA-DR expression on cultured normal keratinocytes. Thus, the high expression of UM4D4 on T-cells in psoriatic skin provides an alternative mechanism for T-cell activation that may be operative in the psoriatic lesional milieu. Indeed, activation of lesional T-cells through the UM4D4 molecule resulted in release of lymphokines that directly induced keratinocytes to express a phenotype displayed in psoriatic skin lesions.

Phenotype, ultrastructure, and function of CD1+DR+ epidermal cells that express CD36 (OKM5) in cutaneous T-cell lymphoma.

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 CD1+DR+ APC. This population was heterogeneous and comprised both leucocytes of a novel CD1+DR+CD36 (OKM5)+ phenotype and CD1+DR+CD36- indeterminate/Langerhans cells. The CD1+DR+CD36+ leucocytes did not express TcR-1, CD5, CD15, or CD22, and only a minor population expressed CD11, demonstrating that they were neither T nor B cells, and did not belong to 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 alloantigens 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 CD1 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.

Fatal cutaneous T cell lymphoma in a child with atopic dermatitis.

The development of a fatal cutaneous T cell lymphoma in a child with atopic disease is presented. From very early childhood the patient had classic atopic dermatitis, and at age 13 developed lymphoma-like skin tumors. The diagnosis--based on immunohistologic criteria--was initially difficult to establish, but cytogenetic and DNA studies of the dermal infiltrate supported the clinical suspicion of malignancy. In addition, the T cell receptor beta chain gene showed a clonal rearrangement pattern both in skin and in lymph node, suggesting malignancy. Whether the malignant evolution in our patient took place primarily in the skin or in the lymph nodes is difficult to decide. Further examination of the association between atopic dermatitis and cutaneous T cell lymphoma may lead to insights into both disorders.