MOLECULAR MECHANISMS INVOLVED IN INTRAEPITHELIAL LYMPHOCYTE MIGRATION- A COMPARATIVE-STUDY IN SKIN AND TONSIL

Intraepithelial lymphocyte migration is a biological process frequentl y observed in skin and tonsil. Using immunohistochemistry, we have stu died the molecular bases of this process in seven skin biopsies involv ed by mycosis fungoides (MF) and in 12 tonsils, four involved by B-chr onic lymphocytic leukaemia (B-CLL) and eight by lymphoid follicular hy perplasia (LH). In the skin, intraepidermal T-lymphocyte infiltration was associated with narrowing and fragmentation of the basement membra ne, as shown by an anti-collagen type IV antibody. Immunostaining of s erial sections with an anti-collagenase type IV antibody revealed that collagenase type IV was localized in the upper dermis and strictly co -distributed with collagen type IV, suggesting that enzymatic digestio n played a role in the alterations of the basement membrane. Further m igration through the epidermis was mediated by expression on keratinoc ytes of intercellular adhesion molecule-1 (ICAM-1) and of leukocyte-fu nction associated antigen-1 (LFA-1) on infiltrating lymphocytes. In th e tonsil, intraepithelial infiltration was mediated by the expression of vascular cell adhesion molecule-1 (VCAM-1) by epithelial cells and of very late antigen-4 (VLA-4) by infiltrating lymphocytes. Further in traepithelial lymphocyte migration was then established, as already sh own in the skin, by ICAM-1/LFA-1 interaction. Lymphocyte recruitment f rom the systemic circulation was studied using antibodies directed aga inst endothelial leukocyte adhesion molecule-1 (ELAM-1), ICAM-1, and V CAM-1. These adhesion molecules were highly expressed by blood vessels in the Lipper dermis of MF and the percentage of ELAM-1 +/VCAM-1 + ve ssels was significantly higher than that observed in tonsils. Our data suggest that distinct molecular mechanisms are used by lymphocytes in intraepithelial migration in the skin and in tonsils.