Molecular mechanisms involved in intraepithelial lymphocyte migration: A comparative study in skin and tonsil

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Abstract
Intraepithelial lymphocyte migration is a biological process frequently observed in skin and tonsil. Using immuno‐histochemistry, we have studied the molecular bases of this process in seven skin biopsies involved by mycosis fungoides (MF) and in 12 tonsils, four involved by B‐chronic lymphocytic leukaemia (B‐CLL) and eight by lymphoid follicular hyperplasia (LH). In the skin, intraepidermal T‐lymphocyte infiltration was associated with narrowing and fragmentation of the basement membrane, as shown by an anti‐collagen type IV antibody. Immunostaining of serial 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 digestion played a role in the alterations of the basement membrane. Further migration through the epidermis was mediated by expression on keratinocytes of intercellular adhesion molecule‐1 (ICAM‐1) and of leukocyte‐function associated antigen‐1 (LFA‐1) on infiltrating lymphocytes. In the 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 intraepithelial lymphocyte migration was then established, as already shown in the skin, by ICAM‐1/LFA‐1 interaction. Lymphocyte recruitment from the systemic circulation was studied using antibodies directed against endothelial leukocyte adhesion molecule‐1 (ELAM‐1), ICAM‐1, and VCAM‐1. These adhesion molecules were highly expressed by blood vessels in the upper dermis of MF and the percentage of ELAM‐1 +/VCAM‐1 + vessels 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.

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