EXPRESSION OF FUNCTIONALLY ACTIVE ALPHA(4)BETA(1) INTEGRIN BY THYMIC EPITHELIAL-CELLS

We have investigated the expression and function of the VLA-4 heterodi mer alpha(4) beta(1), a member of the beta(1) integrin subfamily, on h uman thymic epithelial cells (TEC) derived from cortical epithelium. T he expression of the alpha(4) integrin chain was studied in four diffe rent cloned TEC lines derived from either fetal or post-natal human th ymus by both flow cytometry and immunoprecipitation techniques with an ti-alpha(4) MoAbs. All different cell lines assayed expressed signific ant levels of alpha(4), as revealed by their reactivity with MoAbs spe cific for distinct alpha(4) epitopes. The alpha(4) subunit expressed b y TEC was associated to beta(1) but not to beta(7) chain, and displaye d the characteristic 80/70 kD pattern of proteolytic cleavage. The VLA -4 integrin in these cells was constitutively active in terms of adhes iveness to both fibronectin and vascular cell adhesion molecule-1 (VCA M-1). In addition, this heterodimer localized to punctate regions of t he cell in the area of contact with the substratum, named point contac ts assessed by staining with the anti-beta(1) activation epitope 15/7 MoAb. According to the cortical origin of the TEC lines expressing VLA -4, human thymus sections stained with different anti-alpha(4) antibod ies revealed the presence of cortical, and in smaller numbers medullar y epithelial cells bearing alpha(4) integrin. The expression of alpha( 4) in the thymus was also found in both adult and fetal rats, in which epithelial cells were also specifically stained. Altogether, our data show that VLA-4 is an additional component of the integrin repertoire of TEC, and suggest that it could have an important role in thymus ep ithelial cell-thymocyte interactions.