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The thymic nurse cell complex: an in vitro model for extracellular matrix-mediated intrathymic T cell migration
D M Villa-Verde1, V Mello-Coelho, J M Lagrota-Cândido
1Laboratório de Pesquisas sobre o Timo, Departamento de Imunologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ, Brasil.
Abstract:
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 extracellular matrix (ECM) components. The thymic epithelial cells are the major cellular component of the thymic microenvironment, and influence different aspects of thymocyte differentiation, via cell-cell interactions and secretions of soluble factors, such as thymic hormones. The thymic nurse cell (TNC) complexes are multicellular lymphoepithelial structures formed by one thymic epithelial cell harboring 2-200 thymocytes, primarily bearing the CD4/CD8 double-positive phenotype. TNCs probably create a special microenvironment for thymocyte differentiation and/or proliferation, with thymocytes being exposed to major histocompatibility complex (MHC) antigens and thymic hormones. Such differentiation parallels cell migration into and out of the complex. We showed the expression of ECM components and respective receptors by TNCs, and that interactions between the epithelial component of TNC and TNC-lymphocytes can be modulated by ECM components and respective receptors. Moreover, we demonstrated that intrinsic as well as extrinsic biological circuits can be involved in the control of such ECM-mediated thymic epithelial cell (TEC)/thymocyte interactions. For example, interferon-gamma can biphasically modulate the expression of ECM ligands and receptors by TEC, which results in corresponding modulation of their ability to interact with TNC-thymocytes. Additionally, hormones such as triiodothyronine, prolactin and growth hormone can influence the degree of these lymphocyte/epithelial cell adhesive interactions. Lastly, we recently furnished evidence for a de-adhesive mechanism within TNC apparently mediated by galectin 3 (an endogenous soluble beta-galactoside-binding lectin).(ABSTRACT TRUNCATED AT 250 WORDS)