Extracellular-Matrix Components Of The Mouse Thymic Microenvironment .3. Thymic Epithelial-Cells Express The Vla6 Complex That Is Involved In Laminin-Mediated Interactions With Thymocytes

We describe herein the expression of the VLA6 complex by murine thymic epithelial cells (TEC). The immunohistochemical distribution revealed that VLA6 is found in both thymic medullary and subcapsullary areas. Moreover, studies by immunoelectron microscopy revealed a membrane labeling of the VLA6 molecule, including at desmosomal sites. By means of immunoblotting, immunoprecipitation, and affinity chromatography of extracts from a mouse TEC line, we further demonstrated that VLA6 is a laminin (LN) receptor in these cells. In keeping with this finding, we showed that TEC adhesion, spreading, and proliferation were enhanced in vitro by LN. The fact that VLA6 is also expressed by the large majority of thymocytes raised the hypothesis that it might be involved in LN-mediated TEC-thymocyte interactions. Interestingly, in vitro experiments showed that there is an increase in the TEC-thymocyte adhesion upon glucocorticoid hormone treatment, a situation in which the expression of VLA6 as well as LN is enhanced. Most importantly, this adhesion can be reversed by pre-treating TEC with an anti-alpha6 integrin mAb. Additionally, spontaneous in vitro thymocyte release by thymic nurse cell complexes was enhanced by LN and partially blocked by anti-alpha6 or anti-beta1 antibodies. Our results suggest that VLA6 is involved in LN-mediated TEC - thymocyte interactions that can be relevant for thymic microenvironmental cell physiology and intrathymic T cell differentiation events.