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 and its relationship with TNF-alpha and IL-12. Blocking experiments demonstrated the IFN-gamma dependence of TNF-alpha production and the significant contribution of IL-12 to IFN-gamma secretion. We studied informative pairs allowing the evaluation of the relative importance of HLA class I and class II antigens. Maximal IFN-gamma secretion allowing discrimination between fully HLA different and identical subjects required 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 enhancement 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.
Toungouz
M
M
Department of Immunology and Transfusion, Hôpital Erasme, Universite Libre de Bruxelles, Belgium.
Denys
C
C
Andrien
M
M
De Groote
D
D
Dupont
E
E
D006680:HLA Antigens / Q000187:drug effects* / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology*; D007959:Lymphocyte Culture Test, Mixed; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma