Thymic epithelial cells mediate a Bcl-2-independent protection of single-positive thymocytes from dexamethasone-induced apoptosis

Author(s)

Jacysyn, J. F. ; Conde-Moscatelli, M. ^[2] ; Barrichello, C. R. C. ; Silva, U. R. ; Macedo, M. S. ; Amarante-Mendes, G. P.

• Document type: Journal article
• Source: Experimental Cell Research; v. 272, n. 2, p. 119-126, Jan. 2002.
• Field of knowledge: Biological Sciences - Immunology

Abstract

Intrathymic maturation of thymocytes is essential for the proper formation of T-cell repertoire. This process involves two major biochemical pathways, one initiated by the recognition of MHC/peptide by the T-cell receptor and the other mediated by glucocorticoids. These hormones seem to affect thymocyte maturation by increasing the threshold of TCR-mediated positive and negative selection, and by inducing apoptosis of nonselected thymocytes. We have previously reported that an SV40-immortalized murine thymic epithelial cell line, namely 2BH4, was able to protect thymocytes from dexamethasone-induced apoptosis. Here we show that this protection is independent of cell-to-cell contact and does not seem to involve a Bcl2-mediated resistance, since incubation of thymocytes with 2BH4 cells or its supernatant does not interfere with the levels of this antiapoptotic molecule. The protection conferred by 2BH4 cells, or by a primary culture of thymic stromal cells, is specific for the CD4(+)CD8(-) and CD4(-)CD8(+) single-positive thymocytes, whereas the broad-spectrum caspase inhibitor z-VAD-fmk blocks apoptosis induced by dexamethasone in all thymocyte subpopulations. Our results suggest that positively selected single-positive thymocytes are still susceptible to glucocorticoid-induced apoptosis but are protected from it through the action of a heat-stable protein(s) released by thymic stromal cells. (AU)