Abstract
In this work, the interaction between a rat cortical thymic epithelial cell (TEC) line (R-TNC.1) with nursing activity and thymocytes as well as BWRT 8 thymocyte hybridoma (TH) cells has been studied. The R-TNC.1 cell line significantly bound thymocytes and TH. Binding was stronger during the first 30 min of cell incubation and was followed by a progressive deadhesion. Among adherent thymocytes the proportion of apoptotic cells increased with culture time which was a consequence of higher capacity of the line for binding of apoptotic than viable cells and induction of apoptosis in a subset of adherent thymocytes. Emperiopolesis activity of this thymic nurse cell (TNC) line was manifested by engulfment of thymocytes as well as TH cells. A subset of viable intra-TNC thymocytes has been triggered to die by apoptosis, whereas other internalized thymocytes have been stimulated to proliferate, as measured by an increase in the percentage of cells in mitosis and higher incorporation of bromodeoxyuridine (BrdU), in comparison to thymocytes cultivated alone. A significant stimulation of proliferation of engulfed TH cells was also observed. The R-TNC.1 cell line efficiently phagocytosed both apoptotic thymocytes and TH, and the process is followed by intra-TNC destruction of ingested cells. Cumulatively, these results suggest different role of the R-TNC.1 clone: phagocytosis of apoptotic cells; induction of apoptotic cell death in a subset of both bound and internalized thymocytes and stimulation of proliferation of a subset of intra-TNC thymocytes or TH cells.
Highlights
Thymic nurse cells (TNC) are specialized epithelial cells that form unique multi-cellular complexes with thymocytes (Wekerle et al, 1980)
We have previously demonstrated that LFA-1 and its ligand ICAM-1 are partly involved in the binding of thymocytes to both cortical, R-TNC.1 and medullary (TE-R2.5) cell lines in the early adhesion phase (30 min) (Colicet al., 1994; 1997)
After prolonged incubation (3 h) inhibitory effects of these mAbs were not observed (Colicet al., 1994; 1997 and our unpublished data). These results are in agreement with those of Lepesant et al (1990) who showed that LFA-1 is involved in stabilization of the early rapid phase of thymocyte adhesion to a murine thymic epithelial cell (TEC) line which constitutively expressed ICAM-1 in culture
Summary
Thymic nurse cells (TNC) are specialized epithelial cells that form unique multi-cellular complexes with thymocytes (Wekerle et al, 1980). Since their first description by Wekerle et al (1980), TNC have been considered as a very intriguing microenvironmental component which may provide an ideal place for T cell differentiation, maturation and education as they express MHC antigens, secrete thymic hormones and cytokines and may present self antigens to very immature thymocytes (Kyewski, 1986; Rieker et al, 1995). Very little is known about the nature and mechanisms of the interaction between TNC and thymocytes. This may be due to the fact that it was difficult to obtain the large number of cells needed for experiments. In the past few years this problem has been resolved by establishing thymic epithelial cell (TEC) lines with nursing activity, isolated from spontaneously growing murine thymic tumors or normal thymus by means of various cloning techniques or immortalization procedures by treating the cells with Simian virus 40 (Nishimura et al, 1990; Ezaki et al, 1991; Li et al, 1992; Philp et al, 1993; Pezzano et al, 1995; 1996)
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