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

Abstract

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

Absence of β7 integrin results in less graft-versus-host disease because of decreased homing of alloreactive T cells to intestine

“…20 However, though the ␣ E ␤ 7 integrin may also play a role in thymocyte adhesion to thymic epithelial cells, the few studies published to date do not support a central role for ␣ E ␤ 7 in thymocyte development. 17,18 To study the ␤ 7 subunit, we used donor T cells derived from ␤ 7 Ϫ/Ϫ mice. These T cells showed activation, proliferation, and cytotoxicity profiles similar to those of WT donor T cells, so that differences in T-cell infiltration of target organs and GVHD morbidity and mortality could reasonably be attributed to a homing defect rather than to a functional defect in the ␤ 7 Ϫ/Ϫ T cells.…”

“…15,16 The ␣ ⑀ ␤ 7 integrin may also play a role in thymocyte adhesion to thymic epithelial cells. 17,18 The ␣ 4 ␤ 7 integrin interacts specifically with MAdCAM-1 (mucosal addressin cell adhesion molecule-1) on high endothelial venules in the Peyer patches and intestinal lamina propria, 19,20 and it interacts less specifically with VCAM-1 and fibronectin. 21 Circulating lymphocytes in spleen and mesenteric lymph nodes (MLNs) have low levels of ␣ 4 ␤ 7 expression, which may be up-regulated on activation.…”

Phenotypic Characterization of CD3−7+ Cells in Developing Human Intestine and an Analysis of Their Ability to Differentiate into T Cells

“…It is generally thought that CD103 is induced in gut lymphocytes by TGF␤ (47). On the other hand, there is now some evidence that CD103 is expressed on human thymocytes and that interaction with the CD103 ligand, E-cadherin, on thymic stromal cells enhances thymocyte proliferation (48). In the gut, E-cadherin is expressed on epithelial cells, so it is unlikely that CD103 lamina propria cells will have the opportunity to interact with the ligand, unless the cells traffic in and out of the epithelium.…”

Murine CD8+ Recent Thymic Emigrants are αE Integrin-Positive and CC Chemokine Ligand 25 Responsive

“…CCR9 and ␣ E integrin may also be involved in targeted migration and cell-cell interactions important for cell survival and positioning during/after positive selection. For example, ␣ E integrin-E cadherin interactions between thymocytes and thymic epithelial cells have been shown to induce proliferation of thymocytes (34). Also, CCL25 is expressed on both cortical and medullary epithelium in the thymus, possibly directing migrations of less mature cortical thymocytes as well as more mature medullary CD8 SP cells (35).…”