Interferon-gamma is produced by activated immature mouse thymocytes and inhibits the interleukin 4-induced proliferation of immature thymocytes

Abstract

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.