A MECHANISM UNDERLYING SYNERGY BETWEEN IL-12 AND IFN-GAMMA-INDUCING FACTOR IN ENHANCED PRODUCTION OF IFN-GAMMA

IL-12 and IFN-gamma-inducing factor (IGIF) have the capacity to stimul ate IFN-gamma production by T cells, Using an IL-12-responsive T cell clone, 2D6, we investigated how these two cytokines collaborate for IF N-gamma production, 2D6 obtained from cultures containing rIL-12 produ ced IFN-gamma in response to rIGIF, 2D6 from cultures deprived of IL-1 2 for 24 h produced only marginal revels of IFN-gamma production follo wing stimulation with either rIL-12 or rIGIF alone, However, simultane ous stimulation of these 2D6 cells with both cytokines resulted in str ikingly enhanced levers of IFN-gamma production, 2D6 could also be mai ntained in the presence of rIL-2 instead of rIL-12. 2D6 lines maintain ed with rIL-12 (2D6(IL-12)) Or rIL-2 (2D6(IL-2)) exhibited differentia l IGIF responsiveness: both lines responded similarly to rIL-2 or rIL- 12, whereas the 2D6(IL-12) or 2D6(IL-2) exhibited high or marginal IGI F responsiveness, respectively, The 2D6(IL-12) line expressed IGIF rec eptor (IGIFR), whereas the 2D6(IL-2) did not, Overnight exposure of th e 2D6(IL-12) to rIL-2 reduced IGIFR expression and conversely, exposur e of the 2D6(IL-2) to rIL-12 restored IGIFR expression, IGIFR expressi on by these 2D6 lines correlated with the capacity to produce IFN-gamm a in response to rIGIF, Purified naive T cells stimulated with anti-CD 3 plus anti-CD28 mAb and subsequently cultured with rIL-12 were also f ound to express IGIFR and induce enhanced IFN-gamma production followi ng IGIF stimulation, These results indicate that the induction of IGIF R by IL-12 represents one of the mechanisms underlying the synergy bet ween IL-12 and IGIF in IFN-gamma production.