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 alpha(E)(CD103)beta(7) 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.
Kutlesa
Snjezana
S
University Medical Clinic, Section for Transplantation Immunology and Immunohematology, Tübingen, Germany.
Wessels
Johannes T
JT
Speiser
Angelika
A
Steiert
Inge
I
Müller
Claudia A
CA
Klein
Gerd
G
D015703:Antigens, CD / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D002455:Cell Division; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D039001:Integrin alpha Chains / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D051176:beta Catenin
D015703:Antigens, CD; D016827:CD8 Antigens; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D039001:Integrin alpha Chains; D015534:Trans-Activators; C091367:alpha E integrins; D051176:beta Catenin