Human epidermal Langerhans' cells in bullous pemphigoid

Through the epidermal analysis of 13 patients with bullous pemphigoid compared to controls, using OKT6 monoclonal antibodies on the light microscopic level and electron-microscopy, we found a redistribution of the Langerhans' cells towards the basal membrane in combination with an increased total number of Langerhans' cells. This redistribution was also noted in clinically normal skin from patients with bullous pemphigoid. The findings may be consistent with the theory of antigen presentation.     

Epidermal Langerhans' cells in elderly patients with decubital ulcers

Langerhans' cells in the sacral epidermis 8-10 cm from the lesion of elderly patients (mean age 74 years) with decubital ulcers were studied ultrastructurally and compared with the patients' own normal epidermis from the upper leg, with age-matched normal controls, and with young normal controls (mean age 43 years). High percentages of Langerhans' cells (ranging between 30 and 50%) without dendrites were found in patient epidermis from the sacral region near the lesion and similar percentages in normal skin from the patients' upper leg. In both elderly and young controls, Langerhans' cells without dendrites found in the epidermis of the upper leg were fewer, ranging between 13 and 33%. The density of Langerhans' cells in adjacent sites of the same epidermis was non-homogeneous, being in the range of 0.56-1.19% in patient sacral epidermis, 0.69-1.31% in patient normal leg epidermis, 0.63-4.17% in leg epidermis of the elderly controls, and 0.63-3.94% in leg epidermis of the young controls. The majority of the Langerhans' cells in both patients and controls were located near the basal cell layer and in the mid-epidermis. The percentage of Langerhans' cells found in patient sacral epidermis (0.84 +/- 0.08%) and in their leg epidermis (0.87 +/- 0.15%) was significantly lower than in the elderly controls (1.91 +/- 0.30%) and young controls (1.84 +/- 0.24%). The low percentage of Langerhans' cells in the epidermis of patients with decubital ulcers may affect the healing process of the lesions.     

The epidermal Langerhans' cell population in psoriasis during topical coal tar therapy

We have studied the effect on the Langerhans' cell (LC) population of topical 3% coal tar therapy. Biopsies were taken from psoriatic plaques and from controls with no skin disease before and after the application of 3% coal tar for one week; LC were identified by immunofluorescence using monoclonal antibody. LC counts expressed per unit epidermal surface length were similar in untreated psoriasis plaques and in normal skin. Differences in the LC population in paired biopsies from both patients and controls showed considerable variation following coal tar treatment but no consistent effect could be demonstrated.     

Effect of simulated sunlight on Langerhans' cells in malignant melanoma patients

The effect of artificial sunlight on the number and HLA class II expression of Langerhans' cells was studied in 10 patients with malignant melanoma and 10 control volunteers. The total number of Langerhans' cell decreased in both groups but at 96 h there was a greater and significant decrease (p less than 0.01) in the number of Langerhans' cells in the melanoma group, compared with controls. This decrease persisted and was still greater in the melanoma group (p less than 0.02) at one week post-irradiation. There was a rise in Langerhans' cell count over the following 3 weeks in both groups. Unexpectedly, during this period in the melanoma group-but not controls-there was a significant median peak rise above pre-irradiation levels (p less than 0.001). Alteration in the response of Langerhans' cells to sunlight may play a part in the aetiology of malignant melanoma.     

Langerhans' cells in seborrheic keratosis. A clinical and ultrastructural study

Skin biopsies from 10 patients with seborrheic keratoses were examined by electron microscopy for the presence of Langerhans' cells. Comparing seborrheic keratoses with normal skin of the same patient and with normal skin from controls, neither an increased number of Langerhans' cells nor an increased number of specific granules, Birbeck granules, nor abnormal Langerhans' cells, was found. Melanosomes in a Langerhans' cell were observed in 2 seborrheic keratoses, suggesting phagocytic activity of the Langerhans' cell.     

The presence of IgE molecules on epidermal langerhans cells in patients with atopic dermatitis

Summary Skin sections of clinically involved and clinically normal-looking skin from patients with atopic dermatitis were incubated with anti-human IgE antibodies using the indirect immunoperoxidase technique. Apart from positive dermal anti-IgE staining, positive epidermal anti-IgE staining was also observed. The morphology of the epidermal staining cells suggested the involvement of dendritic cells. This was confirmed by positive immuno-double labelling with OKT6 and anti-IgE. This phenomenon seemed to be specific for atopic dermatitis since skin sections from normal nonatopic controls, patients with allergic asthma, contact dermatitis, and schistosomiasis showed no epidermal anti-IgE staining. To further elucidate the nature of the epidermal anti-IgE staining cells, epidermal cell suspensions were prepared from clinically involved skin from patients with atopic dermatitis. These cell suspensions also showed positive anti-IgE staining cells and positive immuno-double labelling with OKT6 and anti-IgE. Immunogold electron microscopy with anti-IgE on epidermal cell suspensions from patients with atopic dermatitis showed gold particles on the cell membranes of cells containing Birbeck granules, being Langerhans' cells. Epidermal cell suspensions from normal non-atopic controls were negative. The presence of IgE molecules on epidermal Langerhans' cells, which seems to be specific for patients with atopic dermatitis, provides an explanation for the high frequency of positive patch test reactions to inhalant allergens.     

An immunohistochemical staining of epidermal Langerhans' cells in tinea cruris

Epidermal Langerhans' cells (LC) were investigated in fresh cryostat sections of ten biopsies from patients with mycologically proven tinea cruris, using OKT6 monoclonal antibodies and avidin-biotin-immunoperoxidase. Compared to the controls, more epidermal LC and an increased number of LC in the upper half of the epidermis were found in the sections from tinea patients. In a double staining method for both OKT6-positivity and hyphae, a tendency towards a gathering of LC and fungal elements was found. The results of this study are in agreement with the theory that epidermal LC are responsible for the antigen uptake in dermatophytosis.     

Reactive changes in the Langerhans' cells of human skin caused by occlusion with water and sodium lauryl sulphate

Human skin was patch tested with sodium lauryl sulphate or with water only for 48 h and biopsied immediately and after 24 h, then analyzed by immunocytochemistry and electron microscopy. Sodium lauryl sulphate produced a decrease in the number of epidermal Langerhans' cells and an increase in dermal Langerhans' cells, with individual variations. The 48-h water occlusion controls showed only slight reactions. Unexpectedly, quite pronounced reactive changes were seen 24 h after termination of water occlusion. Thus, dermal Langerhans' cells were commonly increased and epidermal Langerhans' cells tended to decrease in number. The results indicate that the 24-h interval is not a period of recovery but a period in which more pronounced reactive changes occur. Hydration over 48 h followed by dehydration leading to temporary damage to the epidermal barrier may explain the present findings. Some of the reactive changes observed after sodium lauryl sulphate exposure probably represent the additive effects of occlusion and sodium lauryl sulphate treatment.     

Langerhans' cells in patients with psoriasis: effect of treatment with PUVA, PUVA bath, etretinate and anthralin

Suction blisters were raised in lesions and normal appearing skin of patients with psoriasis. The blister roof which contains the epidermis separated at the dermal-epidermal junction was stained with ATPase, OKT-6 and anti-HLA-DR monoclonal antibodies. The technique permits the counting of the Langerhans' cells per mm2. Their mean number varied between 888-987 cells per mm2 in control subjects with the three staining procedures. In patients with psoriasis, the number of cells before treatment was between 1110-1179 in uninvolved skin and 521-1001 per mm2 in the lesions as measured using both monoclonal antibodies and ATPase. However, the latter technique seemed to be inappropriate for lesional skin. After treatment with PUVA bath or oral PUVA with or without etretinate, fewer Langerhans' cells were seen in both lesions and normal appearing skin with the appearance of giant Langerhans' cells with long dendrites. In patients healed with anthralin + UV-B the Langerhans' cells appeared normal in number and size.     

Expression of the high affinity IgE-receptor on human Langerhans' cells. Elucidating the role of epidermal IgE in atopic eczema.

Epidermal Langerhans' cells have previously been shown to bear IgE molecules, particularly in atopic dermatitis skin. Using two highly specific antibodies against the antibody-binding chain of the high affinity IgE-receptor, 29C6 and 6F7, we here provide evidence that Langerhans' cells express this receptor in both normal skin (foreskin) and in lesional skin of patients with atopic and stasis eczema. A specific antibody against the low affinity IgE-receptor, Tü1, showed only a low expression of this receptor. This finding has important potential functional implications for the role of Langerhans' cells in transepidermal, IgE-mediated allergy.     

Langerhans' cells in hair follicles of the depigmenting C57Bl/Ler-vit.vit mouse. A model for human vitiligo

The C57Bl/Ler-vit.vit mouse grows a black pelage after birth. During successive hair molts, the fur loses its pigmentation. By 6 months of age, most of the fur of the animal is white. The epidermis of the ears and tail also loses its pigmentation. Histologic studies confirm that in the epidermis and hair follicles there is an absence of pigment cells identifiable by various histochemical or electron microscopic techniques. This mouse may be an excellent model in which to study the role of Langerhans' cells and the immune response in the pathogenesis of vitiligo, a study not easily done in humans. From results of prior studies, we postulated that if Langerhans' cells were involved in the destruction of melanocytes, they would be abnormal (either more or less numerous) in number during the active phase of depigmentation and normal in number after depigmentation was complete. To determine whether the Langerhans cell (Ia+/adenosine triphosphatase dendritic epidermal cell) might be involved in destruction of pigment cells, we quantified the number of Ia+ and adenosine triphosphatase dendritic cells in the hair follicles in skin from the ear, abdomen, back, and tail from male C57Bl/Ler-vit.vit mice while the fur and skin were depigmenting and after depigmentation was almost completed. We found that Langerhans' cells were normal in number during depigmentation and were most numerous after depigmentation. Previous studies indicate that Langerhans' cells in these mice are functionally defective and respond poorly to some contact allergens. From these morphologic and functional data, we conclude that Langerhans' cells probably are uninvolved in causing depigmentation in these mice. We also observed that the epithelium of hair follicles has a significantly higher (up to 1600/mm2) population density of Langerhans' cells than interfollicular skin.     

Variations in the number and morphology of Langerhans' cells in the epidermal component of squamous cell carcinomas

We investigated the number and morphology of Langerhans' cells in the epidermal component of squamous cell carcinomas located on the sun-exposed skin of 10 patients. Using adenosine triphosphatase-stained epidermis from the tumors, we compared the Langerhans' cells in squamous cell carcinoma with those in nontumorous skin specimens from the same patient. The nontumorous skin specimen was obtained from either sun-exposed perilesional or non-sun-exposed sites. In three patients a normal number and almost normal morphology of Langerhans' cells were observed within the epidermal component of the tumor. One patient showed a normal number but a profound alteration of the morphology of the cells. In the remaining six patients, a significant decrease in the number of Langerhans' cells was observed. Langerhans' cells within the epidermal component of the tumors of these patients exhibited morphologic alterations in that they were mainly round or oval rather than highly dendritic. In none of our patients was the number of Langerhans' cells in the tumor increased. We conclude that a decreased number and altered morphology of Langerhans' cells occur in some, but not all, squamous cell carcinomas of the skin, and that there is no apparent difference between the number of Langerhans' cells in sun-exposed vs unexposed skin from the same individual.     

Clinical, immunohistochemical, and electron-microscopic findings in gold dermatitis

The clinical, immunohistochemical, and electronmicroscopic features of 13 consecutive patients with gold dermatitis were analyzed: 12 developed an eczematous dermatitis and one a lichenoid dermatosis. The patients had received intramuscular sodium aurothiomalate therapy from 1 month to 4 years before the dermatitis broke out. After cessation of gold therapy, the dermatitis persisted for 1-11 months. A relatively sparse perivascular mononuclear cell infiltrate was found in the affected skin in all cases. With immunoperoxidase staining, most of the infiltrating cells were shown to be OKT-4-positive T-helper lymphocytes. A majority of the infiltrating cells were Ia, i.e., HLA class II antigen, positive. Clearly increased numbers of dermal OKT-6-positive Langerhans' cells were also seen. In epidermis, on the contrary, the expression of both OKT-6 and Ia markers on dendritic cells was decreased. However, electron-microscopic examination revealed large numbers of macrophage-like cells and the Langerhans cells were activated, often in apposition to mononuclear cells within the epidermis. No correlation was observed between the immunohistological findings and the amount of gold received, the duration of gold therapy, and the interval between the last gold injection and biopsy, respectively, although peripheral blood eosinophilia was more common during 5-10 months of gold therapy. There were no specific findings in the patients in whom dermatitis lasted several months after discontinuation of the therapy. Our findings support the view that immunological mechanisms operate in the development of gold dermatitis, although the exact mechanisms remain unknown.     

Immediate and delayed hypersensitivity reactions to birch pollen in patients with atopic dermatitis.

We investigated immediate and delayed hypersensitivity to birch pollen in 10 patients with atopic dermatitis (AD) who had experienced a worsening of their eczema during the birch pollen season. The patients were prick- and patch-tested and antigen-induced basophil histamine release and lymphocyte proliferation were measured. 9/10 birch pollen-allergic patients proved positive in the histamine release test and the results correlated with specific IgE levels measured by RAST. Birch pollen antigen induced lymphocyte proliferation in 6/10 patients, but a positive patch test result was obtained in only one case. Both peripheral blood monocytes and purified epidermal Langerhans' cells were able to present birch pollen antigen to T cells, although Langerhans' s cells seemed to function less efficiently in this respect.     

Effect of treatment with salt from the Dead Sea (Tomesa therapy) on epidermal Langerhans cells--a clinical study

Among the therapeutical modes of psoriasis, sea-water baths with salts from the Dead Sea in combination with ultraviolet light (Tomesa therapy) play an important part. In a previous paper, we showed that treatment of isolated murine skin with Tomesa salt solutions resulted in an irreversible decrease of ATPase-positive epidermal Langerhans' cells. Our present study is concerned with the treatment of healthy persons and psoriasis patients with baths containing Tomesa salts, which lead to reduced amounts of detectable Langerhans' cells in the epidermis, as well. Baths containing sodium chloride in comparable concentrations, however, were without effect at all. Our findings demonstrate that the antipsoriatic activity of Tomesa therapy is not only due to physical effects but may also be the result of definable pharmacological actions of the salts on skin cells.     

Langerhans' cell distribution in drug eruption.

The number in and distribution of Langerhans' cells were studied in 11 patients with a maculopapular drug eruption. The Langerhans' cells (LC) were identified with a monoclonal antibody to OKT6 antigen, by employing an immunofluorescence technique. Skin biopsies were taken from lesional and non-lesional skin during the acute stage of the disease. LC in the lesional biopsies increased in number by 66% (p less than 0.001) and displayed more intense staining and more prominent dendrites than did LC from non-lesional skin. Control biopsies, taken from identical sites at least 4 weeks after the eruption disappeared, exhibited a cell distribution similar to the non-lesional acute stage (p = N.S.). Delivery of drugs via the circulation and their distribution into the skin may cause a type IV immune reaction due to LC activation by a drug-carrier complex.     

A controlled study of gold contact hypersensitivity

1203 patients attending for routine patch testing at 3 hospitals and 105 volunteers were tested with 0.5% and 0.05% gold sodium thiosulfate (GST). 38 patients (3.2%) and 5 volunteers (4.8%) had positive patch tests to GST. There were no significant differences between volunteers and patients with respect to age, sex, atopy or exposure to gold in dental restorations, jewellery or through occupation. There were no significant differences in prevalence of GST hypersensitivity in the 3 hospitals, or between patients and controls. This is the 1st controlled study of hypersensitivity to GST, and suggests that routine patch testing to gold is of limited clinical benefit.     

Effects of PUVA and mechlorethamine treatment of psoriatic patients on epidermal Langerhans' cells

Using OKT6 monoclonal antibody, we investigated the number of epidermal Langerhans' cells (LCs) in involved skin from patients with psoriasis, before and after mechlorethamine (HN2) or PUVA treatment. The number of LCs remained at about pretreatment number during three weeks of HN2 treatment alone, though they were reduced after 10 systemic PUVA treatments. Therefore, in contrast to PUVA which influences LCs, HN2 seems to have little effect on LCs. LCs in psoriatic plaques were, in number, 3-4 times less numerous than those in uninvolved, nontreated epidermis.     

Normalized ultraviolet (UV) induction of Langerhans cell depletion and neutrophil infiltrates after artificial UVB hardening of patients with polymorphic light eruption

BACKGROUND: Ultraviolet (UV) B hardening has been widely used as a prophylactic treatment in patients with polymorphic light eruption (PLE). Recent investigations have shown that in patients with PLE Langerhans cells (LCs) and neutrophils display less migration from and to the epidermis after an intense UVB irradiation compared with controls. OBJECTIVES: To investigate the effect of UVB hardening of patients with PLE on their cell migratory responses after intense UVB exposure. METHODS: Thirteen patients with PLE were recruited and UVB provocation testing was performed before entering the study. Among these patients, seven developed PLE rash upon UVB provocation ('UVB-P') and the other six did not respond ('UVB-NP'). Eleven age/sex-matched controls were included. Buttock skin of all included individuals was exposed to 6 minimal erythema doses (MED) of UVB (TL-12 lamps). Biopsies were taken after 24 h and 48 h, together with one control biopsy of unirradiated skin. Patients received total-body UVB hardening therapy consisting of 12 irradiations, on average rising from 10% to 140% of the initial MED in 6 weeks. Subsequently, MEDs were reassessed and biopsies were taken from newly irradiated (6 MED UVB) and unirradiated buttock skin. Skin sections were stained for the presence of LCs, macrophages and neutrophils. The cross-sectional area (in percentage) of positively stained cells within the epidermis was assessed from patients before and after hardening and compared with controls. RESULTS: Before therapy, epidermal LC depletion and neutrophil influx at 48 h after 6 MED were most significantly reduced in 'UVB-P' patients (P = 0.025 and P =0.006, respectively) when compared with controls. 'UVB-NP' patients did not differ significantly from controls. After therapy, there were no longer any significant differences in the cell numbers among these three groups. CONCLUSIONS: UVB hardening significantly improves UV-induced cell migratory responses in patients with PLE. UVB provokability of PLE appears to be most strongly linked to reduced UVB-induced trafficking of LCs and neutrophils, and 'UVB-P' patients show normalization of these responses after UVB hardening.     

Reduced density of T6-positive epidermal Langerhans' cells in uninvolved skin of patients with psoriasis

The Langerhans' cell (LC) density is known to be reduced in skin lesions as compared to uninvolved skin in patients with psoriasis. It is, however, still unsettled whether the LC density in uninvolved psoriatic skin differs from the density in normal skin. We have enumerated epidermal LC in uninvolved skin from 15 patients with stable psoriasis and in 15 healthy subjects. Punch biopsies from non-sunexposed skin from the buttock were taken. Epidermal sheets were separated by EDTA and LC then stained with an indirect immunoperoxidase technique using the mouse monoclonal antibody OKT6. The LC density was significantly reduced in uninvolved skin of patients with psoriasis (mean +/- SD: 375 +/- 37/mm2) as compared to healthy controls (544 +/- 168/mm2) (p less than 0.01). A reduced number of LC in uninvolved psoriatic skin is in accordance with previous reports demonstrating an impaired DNCB reactivity in patients with psoriasis. Whether the reduction in LC density is of pathogenic importance for psoriasis is unknown.