Target cell subpopulations for human thymic epithelial conditioned medium in the mouse thymus

Abstract

Human thymic epithelial conditioned medium (HTECM) increases the reactivity of human and mouse thymocytes to Con A and PHA, and the reactivity of mouse thymocytes in mixed lymphocyte culture and in in vivo graft versus host reaction. In this study target cells for HTECM in subpopulations of mouse thymocytes at various times after hydrocortisone (HC) treatment were investigated. The PHA but not the Con A response of cortisone-resistant thymocytes (Tcr, Day 3 after HC) was augmented by HTECM. Twelve days after HC treatment the thymus contained a population of cells (T12) unresponsive to Con A and PHA and unresponsive to HTECM. This situation remained until Day 17. Between Days 17 and 19 the mitogen response was still very low but HTECM induced a marked increase in mitogen reactivity. After Day 19 the responses gradually returned to normal values. Histologically 12 days after HC the thymus corticomedullary differentiation was completely effaced and it contained an almost homogenous population of immature lymphoid cells. Histology returned to normal 17 days after HC. In the presence of Tcr or lymph node (LN) cells, T12 could be stimulated by mitogens. This response of mixtures of T12 and Tcr or LN cells to mitogen was increased by HTECM. The addition of mitomycin-treated Tcr also resulted in an increase in the mitogen reactivity of T12 by HTECM. From these data we conclude that T12, although very immature, are sensitive to HTECM but regulatory T cells are needed to show this effect as measured by thymidine incorporation.