Using a novel system that supports positive selection in vitro, we have investigated the cellular requirements for this process by testing the ability of individual thymic and nonthymic stromal cell types to support the maturation of CD4+CD8+ thymocytes into CD4+ or CD8+ T cells. We show that thymic cortical epithelial cells are unique in their ability to mediate this maturation, and suggest that in addition to TCR ligation, these cells supply specific signals for positive selection. Moreover, by demonstrating positive selection on ECDI (1-ethyl-3-[3'dimethyl-aminopropyl]-carbodiimide)-fixed epithelial cells in this system, we provide direct evidence that the provision of these signals involves interactions with epithelial cell surface molecules rather than the release of soluble factors.

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