Moll J, Eibel H, Schmid P, Sansig G, Botteri F, Palacios R, Van der Putten H
Department of Biotechnology, Ciba-Geigy Ltd., Freiburg.
Eur J Immunol. 1992 Jun;22(6):1587-94. doi: 10.1002/eji.1830220636.
To dissect mechanisms that co-ordinate specific events in thymopoiesis we have characterized alterations in thymic structure and function caused by expression of a transgene. This gene encodes SV40Tag and is specifically expressed in a subset of thymic epithelial (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 approximately 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 features that 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-beta 3. 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 mRNA in vivo is restricted to a small subset of TE cells in the thymus, our findings reveal a novel specific interaction between thymocytes and a specialized subset of TE cells.
为了剖析在胸腺生成过程中协调特定事件的机制，我们对由转基因表达引起的胸腺结构和功能变化进行了特征描述。该基因编码SV40Tag，在出生前后特异性表达于一部分胸腺上皮（TE）细胞中。结果，永生的TE细胞数量增加，胸腺重量增加（可达3克），胸腺生成得以扩展。后者表现为主要胸腺细胞亚群增加约100倍，外周T细胞计数增加。严重增生的胸腺保留了正常胸腺的许多但并非全部形态特征。同样在移植中，SV40Tag + TE细胞促使胸腺增大（可达8克），并组织形成一个主要具有皮质样特征的组织，其中主要包括SV40Tag + TE细胞、胸腺细胞和巨噬细胞。为了研究永生TE细胞中特定基因功能的表达，我们建立了一个细胞系。Epi - A1细胞系表达主要组织相容性复合体I类和II类、Thy - 1、白细胞介素（IL）- 6、IL - 7、巨噬细胞集落刺激因子以及转化生长因子 - β3的基因。最重要的是，Epi - A1细胞还表达IL - 4受体和c - kit配体（KL），该因子与定向分化因子协同作用，引导祖细胞进入造血谱系。KL mRNA低水平的组成型表达不需要IL - 4，但KL mRNA水平在IL - 4刺激下会显著增加。由于KL mRNA在体内的组成型表达仅限于胸腺中一小部分TE细胞，我们的研究结果揭示了胸腺细胞与特定TE细胞亚群之间一种新的特异性相互作用。
