Langerhans cells, immunomodulation and skin lesions. A quantitative, morphological and clinical study.
The epidermal Langerhans cell (LC) plays an important role in contact hypersensitivity reactions by presenting the antigens to T lymphocytes. LCs may also play a role in defence mechanisms against neo-antigens in skin tumours. Some studies have indicated that the LC population declines with age. Ultraviolet radiation induces a significant reduction in the number of epidermal LCs and most immunosuppressive drugs decrease the number and function of LCs as well. Such alterations in LCs might predispose to the development of skin tumours. To evaluate the importance of LCs in immunosurveillance of skin tumours, the number and the morphology of LCs was investigated in unaffected skin of patients with cutaneous tumours and in immunosuppressed patients. LCs within basal cell carcinoma (BCC) were examined as well. ATPase and CD1a staining was used to visualise LCs. The inflammatory response around BCC was estimated by the expression of HLA-DR+, CD3+ and ICAM-1+ cells. The prevalence of skin tumours was studied in renal transplant recipients on different immunosuppressive treatments such as azathioprine (Aza) and prednisolone (P), cyclosporin (CyA), azathioprine and prednisolone or cyclosporin and prednisolone. We found no difference in LC populations in patients treated with PUVA (psoralen and UVA-radiation) or in patients with skin tumours as compared with controls and no age-related reduction in LC numbers. However, immunosuppressed patients showed a reduced number of LCs, especially those who had received triple drug therapy (CyA+Aza+P). Patients treated with azathioprine and prednisolone (10-25 years) had a high prevalence of multiple warts (40%) and skin tumours (29%). In contrast, warts and skin tumours were not common in patients treated for 5 years with CyA+Aza+P or with CyA+P. Thus, the duration of immunosuppressive treatment seems crucial for the development of warts and skin tumours. However, the reduction in LC numbers was not more pronounced with time or in patients with skin lesions as compared with those without lesions. In the epidermis overlying basal cell carcinoma (BCC) the number of LCs was decreased and their morphology changed as compared with LCs in perilesional skin. These alterations were documented in horizontal sheets as well as in vertical sections of the epidermis analysed by light microscopy and with confocal laser scanning microscopy (CLSM). The latter technique permits a quantitative and morphological analysis of LCs in the same tissue volume. In vertical sections, numerous LCs were observed in the dermis surrounding BCC nests.(ABSTRACT TRUNCATED AT 400 WORDS)
Bergfelt
L
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Department of Dermatology, University of Göteborg, Sweden.
D000251:Adenosine Triphosphatases / Q000276:immunology; D000276:Adjuvants, Immunologic; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D001379:Azathioprine / Q000494:pharmacology / Q000627:therapeutic use; D002280:Basal Cell Carcinoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D015815:Cell Adhesion Molecules / Q000276:immunology; D002461:Cell Line, Transformed; D002465:Cell Movement; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D018799:Intercellular Adhesion Molecule-1; D007801:Langerhans Cells / Q000276:immunology* / Q000473:pathology / Q000528:radiation effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D008875:Middle Aged; D015166:Monitoring, Immunologic; D009368:Neoplasm Transplantation; D009381:Neoplasms, Radiation-Induced / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D011701:PUVA Therapy; D011239:Prednisolone / Q000494:pharmacology / Q000627:therapeutic use; D012867:Skin / Q000276:immunology* / Q000473:pathology / Q000528:radiation effects; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology; D014466:Ultraviolet Rays / Q000009:adverse effects
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D006684:HLA-DR Antigens; D018799:Intercellular Adhesion Molecule-1; D016572:Cyclosporine; D011239:Prednisolone; D000251:Adenosine Triphosphatases; D001379:Azathioprine