Human growth factor for murine interleukin (IL)-9 responsive T cell lines: co-induction with IL-6 in fibroblasts and identification as LIF/HILDA.
Two mouse helper T cell clones that proliferate in response to murine interleukin (IL)-9 could also be grown in conditioned medium of stimulated human connective tissue cells. The activity was not due to known T cell growth factors including human IL-9, which is not effective on mouse cells. This growth-stimulatory activity for TS1 cells (GATS) was co-induced with IL-6 on normal fibroblasts and certain sarcoma cell lines stimulated with IL-1, double-stranded RNA, virus or phorbol ester. However, the conditions for optimal induction and the kinetics of production were found to be different for IL-6 and GATS. GATS from phorbol ester-stimulated human hepatosarcoma cells co-purified with IL-6, but could be separated from it by subsequent cation-exchange fast-protein liquid chromatography and reverse-phase high-performance liquid chromatography. Homogeneous tumor cell-derived GATS was a 25-kDa protein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, whereas IL-6 produced by these cells appeared in its 23-kDa form. Pure GATS was found to be inactive in the B cell hybridoma growth assay for IL-6. Finally, GATS was identified by NH2-terminal sequence analysis of the mature protein as leukemia inhibitory factor or human interleukin for DA cells (LIF/HILDA). The effect of LIF/HILDA on T cells was not mediated by IL-2, IL-4 or IL-9 production. Since this cytokine has not previously been reported to act on T cells, further investigation of its role in T cell activation should be taken into consideration.
Van Damme
J
J
Rega Institute for Medical Research, University of Leuven, Belgium.
Uyttenhove
C
C
Houssiau
F
F
Put
W
W
Proost
P
P
Van Snick
J
J
D000595:Amino Acid Sequence; D002460:Cell Line; D002853:Chromatography, Liquid; D005347:Fibroblasts / Q000378:metabolism; D006131:Growth Inhibitors / Q000302:isolation & purification*; D006133:Growth Substances / Q000096:biosynthesis / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D016906:Interleukin-9 / Q000494:pharmacology*; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000302:isolation & purification*; D008969:Molecular Sequence Data; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000378:metabolism
D006131:Growth Inhibitors; D006133:Growth Substances; D015850:Interleukin-6; D016906:Interleukin-9; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines