title: Thymic stroma-derived T-cell inhibitory factor (TSTIF) 1. TSTIF induces inhibition of antigen-stimulated T-cell proliferation.
abstract: The present study investigates the capacity of the MRL104.8a thymic stromal cell clone to modulate T-cell growth. The culture supernatant (SN) from the MRL104.8a stromal cell monolayer was added to cultures of Th-clones with or without T-cell receptor (TCR) stimulation as provided by antigen (Ag) plus splenic antigen-presenting cells (APC). The results demonstrated that the MRL104.8a SN containing IL-7 activity induced dose-dependent proliferation of Th cells when they were not stimulated with Ag/APC. In contrast, addition of the same SN to cultures of Th cells during stimulation with Ag/APC resulted in potent dose-dependent inhibition of their proliferation. IL-7 contained in the SN was neither responsible for, nor involved in the inhibition event, because the inhibition was not observed with rIL-7 and was not neutralized by anti-IL-7 antibody. The growth inhibition of the Th clone in the presence of Ag plus APC was also induced by IL-10 or TGF-beta. However, the MRL104.8a SN-induced growth inhibition was mediated by a factor distinct from these cytokines, because (1) IL-10 cDNA was not amplified in polymerase chain reaction (PCR) products derived from MRL104.8a cells; (2) TGF-beta cDNA was detected in the PCR products, but only marginal levels of TGF-beta activity in an active form were found in the MRL104.8a SN and the SN-induced inhibition was not prevented by anti-TGF-beta antibody; and (3) addition of rIL-7 to antigen-stimulated cultures containing rTGF-beta or rIL-10 induced IL-7 mediated Th proliferation, whereas the MRL104.8a SN-induced inhibition was still observed in the presence of excess rIL-7. Moreover, this factor, designated thymic stroma-derived T-cell inhibitory factor, was found to have a m.w. of 20-25 x 10(3) and to exhibit heparin-binding property. Thus, these results indicate that the MRL104.8a thymic stromal cell clone produces a potentially novel factor that induces inhibition of antigen-stimulated T-cell proliferation.
authors.affiliation: Biomedical Research Center, Osaka University Medical School, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kita
authors.forename: X G
authors.initials: XG
authors.lastname: Tai
authors.forename: I
authors.initials: I
authors.lastname: Hikita
authors.forename: S
authors.initials: S
authors.lastname: Sogoh
authors.forename: Y
authors.initials: Y
authors.lastname: Nishitani
authors.forename: S
authors.initials: S
authors.lastname: Watanabe
authors.forename: T
authors.initials: T
authors.lastname: Sakata
authors.forename: S
authors.initials: S
authors.lastname: Iwagami
authors.forename: H
authors.initials: H
authors.lastname: Teraoka
authors.forename: M
authors.initials: M
authors.lastname: Ogata
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D002999:Clone Cells; D016207:Cytokines / Q000494:pharmacology; D006131:Growth Inhibitors; D006493:Heparin / Q000378:metabolism; D066298:In Vitro Techniques; D015851:Interleukin-7 / Q000037:antagonists & inhibitors; D008213:Lymphocyte Activation / Q000187:drug effects*; D008222:Lymphokines / Q000494:pharmacology*; D051379:Mice; D008970:Molecular Weight; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology*
chemical_list: D000941:Antigens; D016207:Cytokines; D006131:Growth Inhibitors; D015851:Interleukin-7; D008222:Lymphokines; D006493:Heparin