MHC class II gene silencing in trophoblast cells is caused by inhibition of CIITA expression

PROBLEM: Major histocompatibility complex (MHC) class II molecule expressio n is specifically suppressed on fetal trophoblasts, even in response to int erferon (IFN)-gamma, a potent inducer of MHC class II genes. The suppressio n of class II induction has been suggested to play a role in preventing rej ection of the fetal allograft. The mechanism of this suppression is unknown . METHOD OF STUDY: Human trophoblast cell lines were examined for expression of MHC class II transcription factors and for activity of the IFN-gamma sig naling pathway. Additionally, trophoblast cells were transfected with a vec tor expressing the class II transtictivator, CIITA, and assayed for class I I expression. RESULTS: The MHC class II transcription factors RFX and X2BP and the IFN-ga mma signaling pathway components are expressed constitutively and are funct ional in trophoblasts. However, CIITA expression was absent in trophoblasts and could not be induced by IFN-gamma. Transfection of CIITA into trophobl ast cells resulted in derepression of class II gene expression. CONCLUSIONS: The lack of induction of MHC class II genes in response to IFN -gamma in trophoblast cells is caused neither by the absence of factors tha t bind class II promoters, nor by a lesion in the IFN-gamma signaling pathw ay, but results from a specific inhibition of the CIITA gene.