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doi: 10.1242/10.1242/jcs.00142

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

Snjeana Kutlea¹, Johannes T. Wessels², Angelika Speiser¹, Inge Steiert¹, Claudia A. Müller¹ and Gerd Klein^1,*

¹ University Medical Clinic, Section for Transplantation Immunology and Immunohematology, Tübingen, Germany
² Department of Hematology and Oncology, Children's Hospital, University of Tübingen, Germany

^* Author for correspondence (e-mail: gerd.klein{at}uni-tuebingen.de)

Accepted 2 September 2002

Cadherins are a family of cell adhesion molecules that mainly mediate homotypic homophilic interactions, but for E-cadherin, heterophilic interactions with the integrin _E(CD103)ß₇ have 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.

Key words: Thymus, Cell-to-cell interactions, Cellular differentiation, Cell adhesion molecules, Cadherins

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