EVIDENCE FOR THE IN-VIVO ROLE OF CLASS-II TRANSACTIVATOR IN BASAL ANDIFN-GAMMA INDUCED CLASS-II EXPRESSION IN MOUSE-TISSUE

The class II transactivator (CIITA) is a protein that induces the tran scription of MHC class II genes. We studied the expression of CIITA in vivo, comparing steady state levels of CIITA and class II mRNA in var ious mouse tissues. Many tissues in normal mice contained mRNA for CII TA, correlating with class II mRNA. The basal expression of CIITA and class II mRNA in mice with disrupted IFN-gamma genes (GKO mice) was si milar to that in wild-type mice. Injection of rIFN-gamma strongly indu ced CIITA and class II mRNA: CIITA mRNA increased at 2 hr and declined to baseline by 48 hr, whereas class II mRNA increased at 24 hr and re turned to baseline at 7 days. Proinflammatory stimuli that induce IFN- gamma production (allogeneic cells and LPS) induce CIITA and class II expression in wildtype mice, but not in GKO mice. CIITA induction by I FN-gamma was partially sensitive to cycloheximide, suggesting that ano ther protein is required for CIITA induction. The data suggest that CI ITA is a major regulator of basal and induced class II expression in v ivo.