INTERLEUKIN-12 UNMASKS HLA CLASS-I DIFFERENCES DURING MIXED LYMPHOCYTE-REACTION INDUCED INTERFERON-GAMMA PRODUCTION

We investigated the genetic control of IFN-gamma release during MLR an d its relationship with TNF-alpha and IL-12. Blocking experiments demo nstrated the IFN-gamma dependence of TNF-alpha production and the sign ificant contribution of IL-12 to IFN-gamma secretion. We studied infor mative pairs allowing the evaluation of the relative importance of HLA class I and class II antigens. Maximal IFN-gamma secretion allowing d iscrimination between fully HLA different and identical subjects requi red 5 days. In class I different but DRB1 identical pairs, a moderate but discriminant IFN-gamma release was found. Exogenous IL-12 addition after 24 hours of preactivation by MLR resulted in a marked enhanceme nt of IFN-gamma production at day 2. In pairs differing only by class I antigens, the discriminating capacity was significantly increased as compared to values obtained in absence of IL-12 at day 2 (p < 0.004) and at day 5 (p < 0.004). The crucial role of class I antigens on IFN- gamma release was further substantiated by the blocking action of the W6/32 mAb directed against a monomorphic epitope common to all HLA-A, -B, and -C antigens. We conclude that IFN-gamma production during MLR is under the control of class I antigens. Furthermore, exogenous IL-12 strongly amplifies their influence.