AbstractTo dissect mechanisms that co‐ordinate specific events in thymopoiesis we have characterized alterations in thymic structure and function caused by expression of atransgene. This gene encodes SV40Tag and is specifically expressed in a subset of thymicepithelial (TE) cells around birth. As a result the number of immortal TE cells increases, thymic mass increases (up to 3 g), and thymopoiesis is expanded. The latter is reflected by a ˜ 100‐fold increase of the major thymocyte subsets and increased peripheral T cell counts. Grossly hyperplastic thymi retain many but not all morphological features of a normal thymus. Also in grafts, SV40Tag+TE cells steer expansion (up to 8 g) and organize a tissue with mainly cortex‐like featuresthat includes mainly SV40Tag+TE cells, thymocytes, and macrophages. To investigate expression of specialized gene functions in the immortal TE cells, a cell line was derived. The Epi‐A1 cell line expresses the genes for major histocompatibility complex class I and II, Thy‐1, interleukin (IL)‐6, IL‐7, macrophage‐colony‐stimulating factor, and transforming growth factor‐β3. Most importantly, Epi‐A1 cells also express the IL‐4 receptor and the c‐kit ligand (KL), a factor that, in concert with commitment factors, channels progenitors into hemopoietic lineages. The expression of low constitutive levels of KL mRNA does not require IL‐4, but KL mRNA levels are increased dramatically in response to IL‐4. Since constitutive expression of KL mRNAin vivois restricted to a small subset of TE cells in the thymus, our findings reveal a novel specific interaction between thymocytesand a
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