SllnunaryHuman thymic epithelial (TE) cells produce interleukin loe (Ibloe), I1:1~, and 11:6, cytokines that are important for thymocyte proliferation. The mRNAs for these cytokines are short-lived and are inducible by multiple stimuli. Thus, the steady-state levels for II.-1 and I1:6 mRNAs are critical in establishing the final cytokine protein levels. In this study we have evaluated the effect of epidermal growth factor (EGF), a growth factor for TE cells, and its homologue transforming growth factor oe (TGF-a), on primary cultures of normal human TE cells for the levels of I1:1oe, I1:1~, 1I.-6, and TGF-oe mRNA. We showed that TE cells expressed EGF receptors (EGF-R) in vitro and in vivo, and that treatment of TE cells with EGF or TGF-oe increased II.,1 and II.-6 biological activity and mRNA levels for I1:1oe, IL-lfl, and II-.6. Neither EGF nor TGF-c~ increased transcription rates of I1:1oe, II--18, and I1-.6 genes, but rather both EGF and TGF-ee increased cytokine mRNA stability. By indirect immunofluorescence assay, TGF-oe was localized in medullary TE cells and thymic Hassall's bodies while EGF-R was localized to TE cells throughout the thymus. Thus, TGF-oe and EGF are critical regulatory molecules for production of TE cell-derived cytokines within the thymus and may function as key modulators of human T cell development in vivo.