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.
Schluns
K S
KS
Department of Cell Biology, Neurobiology and Anatomy, Loyola University Chicago Medical Center, Maywood, IL 60153, USA.
Grutkoski
P S
PS
Cook
J E
JE
Engelmann
G L
GL
Le
P T
PT
D000818:Animals; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis; D018076:DNA, Complementary / Q000235:genetics; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004848:Epithelium / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008168:Lung; D008222:Lymphokines / Q000096:biosynthesis / Q000235:genetics; D008907:Mink; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics
D016207:Cytokines; D018076:DNA, Complementary; D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor