Interferon-gamma is produced by activated immature mouse thymocytes and inhibits the interleukin 4-induced proliferation of immature thymocytes.
We have recently shown that interleukin 4 (IL-4) (formerly called BSF-1) is a potent stimulator of fetal and adult immature thymocyte proliferation and that adult L3T4-/Lyt-2-thymocytes can be stimulated by calcium ionophore (A23187) and phorbol ester to secrete IL-4 (Zlotnik, A., J. Ransom, G. Frank, M. Fischer, and M. Howard. 1987. Proc. Natl. Acad. Sci. (USA) 84:3856). This report shows that fetal thymocytes (day 15 of gestation) can also be activated to produce IL-4 suggesting that IL-4 may be a mediator of fetal as well as adult immature thymocyte proliferation. Furthermore, we demonstrate that interferon-gamma (IFN-gamma) inhibits the IL-4-mediated proliferation of both fetal and adult L3T4-/Lyt-2-thymocytes. The inhibition of proliferation is blocked by anti-IFN-gamma antibody and is unaffected by indomethacin suggesting that IFN-gamma directly inhibits immature thymocyte proliferation. IFN-gamma does not block the IL-4/phorbol myristate acetate-mediated proliferation of an adult thymocyte population, which is enriched for L3T4-/Lyt-2+ and L3T4+/Lyt-2- cells, suggesting that the inhibitory effect of IFN-gamma is limited to the immature thymocyte population. Both fetal (day 15) and adult L3T4-/Lyt-2--thymocytes can be activated to secrete an IFN-gamma like activity. This activity is neutralized by a monoclonal anti-IFN-gamma antibody indicating that the activity is due to IFN-gamma. mRNA analysis of adult L3T4-/Lyt-2- thymocytes stimulated with A23187 and phorbol myristate acetate confirms that mRNA for both IL-4 and IFN-gamma is induced in adult L3T4-/Lyt-2- thymocytes. These results indicate that IL-4 and IFN-gamma can regulate immature thymocyte proliferation.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000001:Calcimycin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D015847:Interleukin-4; D007378:Interleukins / Q000096:biosynthesis* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013950:Thymus Gland / Q000196:embryology
D000911:Antibodies, Monoclonal; D007378:Interleukins; D012333:RNA, Messenger; D015847:Interleukin-4; D000001:Calcimycin; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin