Human thymic epithelial cells produce TGF-beta 3 and express TGF-beta receptors.
Copyright policy )Human thymic epithelial cells produce TGF-beta 3 and express TGF-beta receptors.
TGF-beta affects proliferation, differentiation and maturation of T cells; however, the effect of TGF-beta on thymic stromal cells has not been characterized. To better understand the role of TGF-beta in T cell development, we determined whether TGF-beta is present in the human thymus, and identified stromal cells that express TGF-beta receptors and respond to TGF-beta. We demonstrate that primary cultured human thymic epithelial cells (TEC) express TGF-beta 1, TGF-beta 2 and TGF-beta 3, as well as TGF-beta type I receptor (T beta RI) (ALK-5) and TGF-beta type II receptor (T beta RII) transcripts. In vitro, epidermal growth factor (EGF) increases transcript levels of TGF-beta 1, TGF-beta 3 and T beta RII, suggesting that EGF may modulate TGF-beta responses in TEC; however, TGF-beta 2 and T beta RI transcript levels were not affected. We also detect TGF-beta 3 and T beta RII protein in association with keratin-positive TEC in vitro and in vivo. TEC culture supernatants contain TGF-beta 3 as detected by Western blots and, upon heat and acid activation, display growth inhibitory activity on the CCL-64 cells that is neutralized by anti-TGF-beta mAb treatment. We further demonstrate that TGF-beta 1 increases leukemia inhibitory factor transcript levels in TEC, indicating that TEC express functional TGF-beta receptors. Thus, we have shown in the human thymus that TEC produce TGF-beta 3 and express T beta RI and T beta RII. The data suggest that TGF-beta is present in the human thymus and may indirectly affect T cell development by regulating TEC cytokine production.
- University of Chicago Medical Center United States
Lymphokines, DNA, Complementary, Epidermal Growth Factor, Interleukin-6, Infant, Newborn, Infant, Leukemia Inhibitory Factor, Epithelium, Growth Inhibitors, Gene Expression Regulation, Mink, Child, Preschool, Animals, Cytokines, Humans, RNA, Messenger, Child, Lung, Receptors, Transforming Growth Factor beta, Cells, Cultured
Lymphokines, DNA, Complementary, Epidermal Growth Factor, Interleukin-6, Infant, Newborn, Infant, Leukemia Inhibitory Factor, Epithelium, Growth Inhibitors, Gene Expression Regulation, Mink, Child, Preschool, Animals, Cytokines, Humans, RNA, Messenger, Child, Lung, Receptors, Transforming Growth Factor beta, Cells, Cultured
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