ANALYSIS OF THYMIC STROMAL CELL SUBPOPULATIONS GROWN IN-VITRO ON EXTRACELLULAR-MATRIX IN DEFINED MEDIUM .5. PROLIFERATION REGULATING ACTIVITIES IN SUPERNATANTS OF HUMAN THYMIC EPITHELIAL-CELL CULTURES

In previous reports in this series, we described the growth conditions , morphology and supernatant activities of human thymic epithelial cel l cultures. The human thymic epithelial cell supernatant (HTES) contai ned IL-6, G-CSF and M-CSF activities and exhibited a strong enhancing effect on thymocyte proliferative response to mitogens, which was iden tified as IL-6 related. The responding thymocyte population was appare ntly identified as PNA, mature T cells. Tn order to simplify further a nalysis of HTES activities, we selected to use a well-defined mature m urine T cell clone which has a Th2 phenotype (8-5 clone). HTES induced 8-5 cell proliferation without the presence of antigen, antigen prese nting cells (APC) or mitogens. This enhancing effect of HTES was compl etely 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 me diating this effect. HTES induced proliferation was accompanied by end ogenous IL-4 secretion from 8-5 cells. Furthermore, the proliferation was blocked by anti mIL-4 antibody, implicating IL-4 as an autocrine g rowth factor in this system. HTES increased also the expression of IL- 2 receptor. In addition, rhIL-2 and rmIL-4 each had a synergistic effe ct on the proliferative response of 8-5 cells to HTES. A similar syner gistic activity was demonstrated when rhIL-6 was used instead of HTES, suggesting that IL-6 regulates some of HTES activities. Our findings indicate that HTES activities, of which IL-6 is only part, are mediate d via the induction of autocrine growth factors and by the regulation of T cell growth factor receptor expression. (C) 1997 International So ciety for Immunopharmacology.