DISCRIMINATION BETWEEN THYMIC EPITHELIAL-CELLS AND PERIPHERAL ANTIGEN-PRESENTING CELLS IN THE INDUCTION OF IMMATURE T-CELL DIFFERENTIATION

During their intrathymic migration, immature CD4(+) CD8(+) thymocytes that express a TCR able to recognize the expressed MHC molecules are p ositively selected, i.e., complete their differentiation program and b ecome mature T cells. Using the immature CD4(+)CD8(+) T cell line DPK, which can be induced to differentiate in culture, we show here that a subset of isolated thymic epithelial cells, but not peripheral antige n-presenting cells, can induce differentiation, suggesting a unique fu nction of these cells in T cell development. In addition, analysis of activation markers induced by thymic epithelial cells versus specific antigen gives the first direct evidence that positive selection is ass ociated with low level cell activation. In contrast with strict affini ty-avidity models of thymic selection, we propose that a specialized a ntigen-presenting cell environment is an essential contributor to TCR- mediated differentiation in the thymus.