THE UNIQUE ROLE OF INTERFERON-GAMMA IN THE REGULATION OF MHC EXPRESSION ON ARTERIAL ENDOTHELIUM

We examined the expression of MHC class I and II in the arterial endot helium of interferon-gamma (IFN-gamma, GKO) and IFN-gamma-R (IFN-gamma -R, GRKO) gene knockout mice in comparison with mice with intact IFN-g amma and IFN-gamma-R genes, BALB/c and 129Sv/J wild-type, respectively . The GKO and GRKO were produced by gene targeting. MHC class I and II expression was assessed by mAb binding to frozen tissue (kidney, sple en, heart, liver) sections by immunoperoxidase staining in the basal s tate and after various stimuli: allogeneic cells, oxazolone skin sensi tization, LPS, and rIFN-gamma. As controls, we also examined the expre ssion of two other IFN-gamma inducible genes present in the endotheliu m, Ly-6 and ICAM-1. We found that basal class I expression was present in the small arteries and arterioles of BALB/c and 129Sv/J wild-type mice but absent from arterial endothelium of GKO and GRKO mice. Class I was induced in the endothelium of BALB/c and 129Sv/J wild-type mice by three in vivo stimuli: allogeneic, LPS, and oxazolone, whereas clas s II was only induced after allogeneic stimulus. Administration of rIF N-gamma induced class I in the endothelium of GKO and BALB/c wild-type mice. The basal expression of Ly-6 and ICAM-1 was similar in the arte ries of GKO and BALB/c wild-type mice, indicating that, the basal expr ession of these proteins in endothelium is IFN-gamma independent, unli ke class I. In summary, basal class I expression in arterial endotheli um is not constitutive as previously believed, but is dependent on bas al IFN-gamma production. IFN-gamma has an essential role in the induct ion of class I and II expression in arterial endothelium. The fact tha t MHC class I is induced in endothelium may be useful therapeutically for reduction of immune recognition in transplantation.