Expression of functionally active α4β1 integrin by thymic epithelial cells

We have investigated the expression and function of the VLA-4 heterodimer α 4 β 1 , a member of the β 1 integrin subfamily, on human thymic epithelial cells (TEC) derived from cortical epithelium. The expression of the α 4 integrin chain was studied in four different cloned TEC lines derived from either fetal or post-natal human thymus by both flow cytometry and immunoprecipitation techniques with anti-α 4 MoAbs. All different cell lines assayed expressed significant levels of α 4 , as revealed by their reactivity with MoAbs specific for distinct α 4 epitopes. The α 4 subunit expressed by TEC was associated to β 1 but not to β 7 , chain, and displayed the characteristic 80/70 kD pattern of proteolytic cleavage. The VLA-4 integrin in these cells was constitutively active in terms of adhesiveness to both fibronectin and vascular cell adhesion molecule-1 (VCAM-I). In addition, this heterodimer localized to punctate regions of the cell in the area of contact with the substratum, named point contacts assessed by staining with the anti-β 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-α 4 antibodies revealed the presence of cortical, and in smaller numbers medullary epithelial cells bearing α 4 integrin. The expression of α 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 epithelial cell thymocyte interactions.