title: Analysis of thymic stromal cell subpopulations grown in vitro on extracellular matrix in defined medium--V. Proliferation regulating activities in supernatants of human thymic epithelial cell cultures.
abstract: In previous reports in this series, we described the growth conditions, morphology and supernatant activities of human thymic epithelial cell cultures. The human thymic epithelial cell supernatant (HTES) contained IL-6, G-CSF activities and exhibited a strong enhancing effect on thymocyte proliferative response to mitogens, which was identified as IL-6 related. The responding thymocyte population was apparently identified as PNA, mature T cells. In order to simplify further analysis of HTES activities, we selected to use a well-defined mature murine T cell clone which has a Th2 phenotype (8-5 clone). HTES induced 8-5 cell proliferation without the presence of antigen, antigen presenting cells (APC) or mitogens. This enhancing effect of HTES was completely blocked with anti hIL-6 antibody but could not be reproduced by rhIL-6 alone. Hence, IL-6 is a necessary but insufficient factor in mediating this effect. HTES induced proliferation was accompanied by endogenous IL-4 secretion from 8-5 cells. Furthermore, the proliferation was blocked by anti mIL-4 antibody, implicating IL-4 as an autocrine growth factor in this system. HTES increased also the expression of IL-2 receptor. In addition, rhIL-2 and rmIL-4 each has a synergistic effect on the proliferative response of 8-5 cells to HTES. A similar synergistic activity was demonstrated when rhIL-6 was used instead of HTES, suggesting that IL-6 regulates some HTES activities. Our findings indicate that HTES activities, of which IL-6 is only part, are mediated via the induction of autocrine growth factors and by the regulation of T cell growth factor receptor expression.
authors.affiliation: Department of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Meilin
authors.forename: Y
authors.initials: Y
authors.lastname: Sharabi
authors.forename: J
authors.initials: J
authors.lastname: Shoham
mesh_terms: D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016895:Culture Media, Serum-Free; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology*; D004357:Drug Synergism; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D015850:Interleukin-6 / Q000032:analysis / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D018418:Th2 Cells / Q000187:drug effects*; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D000093242:Interleukin-6 Inhibitors
chemical_list: D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D016207:Cytokines; D006133:Growth Substances; D007376:Interleukin-2; D015847:Interleukin-4; D015850:Interleukin-6; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D000093242:Interleukin-6 Inhibitors