Mature Human Thymocytes Migrate on Laminin-5 with Activation of Metalloproteinase-14 and Cleavage of CD44

• Published in: The Journal of immunology (1950) Vol. 172; no. 3; pp. 1397 - 1406
• Main Authors: Vivinus-Nebot, Mylene, Rousselle, Patricia, Breittmayer, Jean-Philippe, Cenciarini, Claire, Berrih-Aknin, Sonia, Spong, Suzanne, Nokelainen, Pasi, Cottrez, Francoise, Marinkovich, M. Peter, Bernard, Alain
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.02.2004; Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists
• Subjects: Biochemistry, Molecular Biology; CD44 antigen; Cell Adhesion Molecules - physiology; Cell Communication - immunology; Cell Differentiation - immunology; Cell Movement - immunology; Cells, Cultured; Enzyme Activation - immunology; Humans; Hyaluronan Receptors - metabolism; Hyaluronan Receptors - physiology; Hydrolysis; Immunophenotyping; Infant; Integrin alpha3beta1 - physiology; Integrin alpha6beta4 - physiology; Kalinin; Laminin - metabolism; laminin-5; Life Sciences; Matrix Metalloproteinases, Membrane-Associated; Metalloendopeptidases - metabolism; Metalloendopeptidases - physiology; Metalloproteinase-14; Peptide Fragments - metabolism; Protein Processing, Post-Translational - immunology; Protein Subunits - metabolism; Solubility; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - enzymology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Thymus Gland - cytology; Thymus Gland - enzymology; Thymus Gland - immunology; Thymus Gland - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.172.3.1397

We have previously shown that laminin-5 is expressed in the human thymic medulla, in which mature thymocytes are located. We now report that laminin-5 promotes migration of mature medullary thymocytes, whereas it has no effect on cortical immature thymocytes. Migration was inhibited by blocking mAbs directed against laminin-5 integrin receptors and by inhibitors of metalloproteinases. Interactions of thymocytes with laminin-5 induced a strong up-regulation of active metalloproteinase-14. However, we found that thymocytes did not cleave the laminin-5 gamma(2) chain, suggesting that they do not use the same pathway as epithelial cells to migrate on laminin-5. Interactions of thymocytes with laminin-5 also induced the release of a soluble fragment of CD44 cell surface molecule. Moreover, CD44-rich supernatants induced thymocyte migration in contrast with supernatants depleted in CD44 by immunoadsorption. CD44 cleavage was recently reported to be due to metalloproteinase-14 activation and led to increased migration in cancer cells. Thus, in this study, we show that laminin-5 promotes human mature thymocyte migration in vitro via a multimolecular mechanism involving laminin-5 integrin receptors, metalloproteinase-14 and CD44. These data suggest that, in vivo, laminin-5 may function in the migration of mature thymocytes within the medulla and be part of the thymic emigration process.