HUMAN THYMIC EPITHELIAL-CELLS PRODUCE TGF-BETA-3 AND EXPRESS TGF-BETARECEPTORS

TGF-beta affects proliferation, differentiation and maturation of T ce lls; however, the effect of TGF-beta on thymic stromal cells has not b een characterized. To better understand the role of TGF-beta in T cell development, we determined whether TGF-beta is present in the human t hymus, and identified stromal cells that express TGF-beta receptors an d respond to TGF-beta. We demonstrate that primary cultured human thym ic 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-bet a type II receptor (T beta RII) transcripts. In vitro, epidermal growt h factor (EGF) increases transcript levels of TGF-beta 1, TGF-beta 3 a nd 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 affe cted. We also detect TGF-beta 3 and T beta RII protein in association with keratin-positive TEC in vitro and in vivo. TEC culture supernatan ts contain TGF-beta 3 as detected by Western blots and, upon heat and acid activation, display growth inhibitory activity on the CCL-64 cell s that is neutralized by anti-TGF-beta mAb treatment. We further demon strate that TGF-beta 1 increases leukemia inhibitory factor transcript levels in TEC, indicating that TEC express functional TGF-beta recept ors. 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-bet a is present in the human thymus and may indirectly affect T cell deve lopment by regulating TEC cytokine production.