Only dull CD3⁺ thymocytes bind to thymic epithelial cells. the binding is elicited by both CD2/LFA‐3 and LFA‐1/ICAM‐1 interactions

Abstract

In view of the necessity for thymocytes to interact with thymic epithelial cells to differentiate into mature T cells, this study analyzed the binding between human thymocytes, cultured thymic epithelial cells (CTEC) and the required adhesion molecules. Immediately after separation, thymic epithelial cells (TEC) readily expressed ICAM-1, which is one of the ligands of LFA-1 cell adhesion molecules. However, the ICAM-1 expression was gradually lost upon culture of TEC. IFN-gamma re-induced ICAM-1 on the CTEC, and the ability of CTEC to bind to thymocytes was also increased by IFN-gamma treatment. The increase in binding seemed to be caused by the LFA-1/ICAM-1 interaction, since it was inhibited by anti-ICAM-1 monoclonal antibody (mAb) and anti-LFA-1 mAb. This suggests that the LFA-1/ICAM-1 interaction is also involved in vivo with the binding of thymocytes to TEC, which have been shown to express ICAM-1. To better understand the nature of the cells involved in binding, thymocytes were sorted into CD3-, CD3dull+, and CD3bright+ subsets (which are supposed to represent the immature, intermediate and mature stages of differentiation, respectively), and were examined for their binding to IFN-gamma-treated CTEC. The result showed that only the CD3dull+ subset bound to CTEC. CD3-, CD3bright+ cells and peripheral blood T lymphocytes did not bind, but they were induced to bind by neuramidase treatment All these bindings were inhibited by anti-LFA-1 mAb and anti-CD2 mAb. These findings indicate that CD3dull+ cells can bind to TEC via CD2/LFA-3 and LFA-1/ICAM-1 interactions. Other cells seemed not to bind to TEC because of sialylation.

Thymic Nurse Cells Forming a Dynamic Microenvironment in Spontaneous Thymoma BUF/Mna Rats.

“…Among these, ICAM-1 was shown to be strongly expressed on almost all TNCs, and some TNCs contained cells with either LFA-la or LFA-1B markers, the ligands for ICAM-1. In vitro studies have also revealed that classical cell adhesion molecules (ICAM-1) can mediate intrathymic T cell migration and differentiation (NONOYAMA et al, 1989;SINGER et al, 1990). Although laminin was only faintly expressed in the TNCs, it may also mediate the cell traffic within TNCs, since typical extracellular matrices (fibronectin, laminin) are known to mediate the release of thymocytes from TNCs (SAVINO et al, 1993;VILLA-VERDE et al, 1994).…”

Expression, function and regulation of the intercellular adhesion molecule‐1 (ICAM‐1) on human intestinal epithelial cell lines

“…Non-hematopoietic cells such as epithelial cells of the skin [ll],the thymus [12] and the thyroid [13] can be inducedfor ICAM-1 expression by cytokines such as IFN-y, I L l p and TNF-a. In vivo, gut epithelial cells, like keratinocytes, do not constitutively express detectable amounts of ICAM-1 ( [9] and D. Kaiserlian, unpublished).…”

Defective signal transduction by the CD2 molecule in immature T-cell receptor/CD3- thymocytes.

“…(ii) Treatment of embryonic thymus in organ culture or in vivo injection of newborn mice with anti-CD2 mAb does not interfere with normal thymocyte differentiation (29,31). (iii) Only TCR/ CD3+ cells have been shown to bind to thymic epithelial cells through a CD2-LFA-3 interaction or to be stimulated as a result of this interaction (32).…”