EXTRACELLULAR-MATRIX COMPONENTS OF THE MOUSE THYMUS MICROENVIRONMENT .5. INTERFERON-GAMMA MODULATES THYMIC EPITHELIAL CELL THYMOCYTE INTERACTIONS VIA EXTRACELLULAR-MATRIX LIGANDS AND RECEPTORS/

Extracellular matrix (ECM) proteins influence cell migration and diffe rentiation in a variety of cell systems. Within the thymus, the ECM di stribution pattern is conserved among various mammalian species, but i ts physiological role is not completely understood. Interferon-gamma ( IFN-gamma), a cytokine produced by thymocytes, is able to in vitro mod ulate ECM production by thymic epithelial cells (TEC) in a dose-depend ent biphasic pattern. In the same model, we determined herein that the expression of VLA-5 and VLA-6 (fibronectin and laminin receptors, res pectively) were upregulated by low doses of IFN-gamma, whereas high do ses of the cytokine induced an opposite effect. In a second in vitro s ystem, we evidenced that thymocyte adhesion to a TEC line was also mod ulated by IFN-gamma. Importantly, such effects were due to the biphasi c modulation of ECM ligands and receptors since they could be specific ally prevented by preincubating the TEC cultures with anti-ECM or anti -ECM receptor antibodies, Additionally, spontaneous thymocyte release from thymic nurse cells was similarly biphasically modulated by IFN-ga mma. Our data provide support for the notion that thymocyte-derived pr oducts can play a role in the dialogue that exists in the thymus, envo lving differentiating thymocytes and microenvironmental cells, Moreove r, we bring arguments indicating that one of the implicated mechanisms involved is the modulation of ECM ligands and receptors by the thymic epithelium. (C) 1996 Academic Press, Inc.