IL-12 INDUCES GROWTH OF THE IL-4-DEPENDENT CT4S LINE AND HAS A SYNERGISTIC EFFECT ON IL-4-INDUCED CT4S PROLIFERATION

In the course of studies designed to explore the effect of interleukin 12 (IL-12) on the development of experimental autoimmune uveoretiniti s (EAU), we observed that supernatants from IL-12-treated cultures of ocular antigen-specific lymphocytes induced proliferation of the inter leukin 4 (IL-4)-dependent CT4S line. This result was surprising, as th ese supernatants were not expected to contain high levels of IL-4. We therefore explored the possibility that IL-12 itself, that remained in the supernatants, could induce proliferation of CT4S cells. In this s eries of experiments we demonstrate that CT4S cells proliferate to rec ombinant as well as to naturally produced IL-12, and that IL-4 and IL- 12 synergize in supporting proliferation of CT4S cells. The proliferat ion induced by IL-12, as well as the synergistic effect with IL-4, can be reversed by neutralizing anti-IL-12 antibodies. Proliferation of C T4S can be abrogated completely by a combination of antibodies against IL-4 and IL-12. Our data have important implications for the use of C T4S as a specific bioassay for IL-4, since both IL-4 and IL-12 may be found together in at least some culture supernatants. Furthermore, our results suggest that the CT4S line (or a derivative selected from it) could be used as a bioassay for detection of IL-12 in combination wit h the specific antibodies.