Developmentally regulated interactions of human thymocytes with different laminin isoforms

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Abstract
The gene family of heterotrimeric laminin molecules consists of at least 15 naturally occurring isoforms which are formed by five different α, three β and three γ subunits. The expression pattern of the individual laminin chains in the human thymus was comprehensively analysed in the present study. Whereas laminin isoforms containing the laminin α1 chain (e.g. LN-1) were not present in the human thymus, laminin isoforms containing the α2 chain (LN-2/4) or the α5 chain (LN-10/11) were expressed in the subcapsular epithelium and in thymic blood vessels. Expression of the laminin α4 chain seemed to be restricted to endothelial cells of the thymus, whereas the LN-5 isoform containing the α3 chain could be detected on medullary thymic epithelial cells and weakly in the subcapsular epithelium. As revealed by cell attachment assays, early CD4− CD8− thymocytes which are localized in the thymus beneath the subcapsular epithelium adhered strongly to LN-10/11, but not to LN-1, LN-2/4 or LN-5. Adhesion of these thymocytes to LN-10/11 was mediated by the integrin α6β1. During further development, the cortically localized CD4+ CD8+ thymocytes have lost the capacity to adhere to laminin-10/11. Neither do these cells adhere to any other laminin isoform tested. However, the more differentiated single positive CD8+ thymocytes which were mainly found in the medulla were able to bind to LN-5 which is expressed by medullary epithelial cells. Interactions of CD8+ thymocytes with LN-5 were integrin α6β4-dependent. These results show that interactions of developing human thymocytes with different laminin isoforms are spatially and developmentally regulated.