E-cadherin-mediated interactions of thymic epithelial cells with CD103⁺ thymocytes lead to enhanced thymocyte cell proliferation

Cadherins are a family of cell adhesion molecules that mainly mediate homotypic homophilic interactions, but for E-cadherin, heterophilic interactions with the integrin α_E(CD103)β₇have also been reported. In the human thymus, where thymocytes develop in close contact with thymic stromal cells, E-cadherin expression was detected on thymic epithelial cells. By immunofluorescence staining, the strongest expression of E-cadherin was observed on medullary thymic epithelial cells. These cells also express cytosolic catenins, which are necessary to form functional cadherin-catenin complexes. Regardless of their developmental stage, human thymocytes do not express E-cadherin, indicating that homophilic interactions cannot occur. Flow cytometric analysis revealed that the E-cadherin ligand CD103 is expressed on subpopulations of the early CD4^- CD8^- double-negative and of the more mature CD8⁺ single-positive thymocytes. Using an in vitro cell adhesion assay, double-negative and CD8⁺ single-positive thymocytes adhered strongly to isolated thymic epithelial cells. These adhesive interactions could be inhibited by antibodies against E-cadherin or CD103. CD8⁺thymocytes showed a proliferative response when incubated with thymic epithelial cells. This mitogenic effect was inhibited by antibodies against CD103, which strongly indicates a direct involvement of the adhesive ligand pair CD103—E-cadherin in human thymocyte cell proliferation.