THE THYMIC NURSE CELL COMPLEX - AN IN-VITRO MODEL FOR EXTRACELLULAR MATRIX-MEDIATED INTRATHYMIC T-CELL MIGRATION

The thymus is a primary lymphoid organ in which bone marrow-derived T cell precursors undergo a complex maturation process in the context of the thymic microenvironment, represented by non-lymphoid cells and ex tracellular matrix (ECM) components. The thymic epithelial cells are t he major cellular component of the thymic microenvironment, and influe nce different aspects of thymocyte differentiation, via cell-cell inte ractions and secretion of soluble factors, such as thymic hormones. Th e thymic nurse cell (TNC) complexes are multicellular lymphoepithelial structures formed by one thymic epithelial cell harboring 2-200 thymo cytes, primarily bearing the CD4/CD8 double-positive phenotype. TNCs p robably create a special microenvironment for thymocyte differentiatio n and/or proliferation, with thymocytes being exposed to major histoco mpatibility complex (MHC) antigens and thymic hormones. Such different iation parallels cell migration into and out of the complex. We showed the expression of ECM components and respective receptors by TNCs, an d that interactions between the epithelial component of TNC and TNC-ly mphocytes can be modulated by ECM components and respective receptors. Moreover, we demonstrated that intrinsic as well as extrinsic biologi cal circuits can be involved in the control of such ECM- mediated thym ic epithelial cell (TEC)/thymocyte interactions. For example, interfer on-gamma can biphasically modulate the expression of ECM ligands and r eceptors by TEC, which results in corresponding modulation of their ab ility to interact with TNC-thymocytes. Additionally, hormones such as triiodothyronine, prolactin and growth hormone can influence the degre e of these lymphocyte/epithelial cell adhesive interactions. Lastly, w e recently furnished evidence for a de-adhesive mechanism within TNC a pparently mediated by galectin 3 (an endogenous soluble beta galactosi de-binding lectin). Taken together, our data strongly indicate that th ymic nurse cells can be regarded as an in vitro model for intrathymic T cell mig ration, particularly with respect to those events mediated by the extracellular matrix.