MHC class II gene silencing in trophoblast cells is caused by inhibition of CIITA expression.
OBJECTIVE
Major histocompatibility complex (MHC) class II molecule expression is specifically suppressed on fetal trophoblasts, even in response to interferon (IFN)-gamma, a potent inducer of MHC class II genes. The suppression of class II induction has been suggested to play a role in preventing rejection of the fetal allograft. The mechanism of this suppression is unknown.


METHODS
Human trophoblast cell lines were examined for expression of MHC class II transcription factors and for activity of the IFN-gamma signaling pathway. Additionally, trophoblast cells were transfected with a vector expressing the class II transactivator, CIITA, and assayed for class II expression.


RESULTS
The MHC class II transcription factors RFX and X2BP and the IFN-gamma signaling pathway components are expressed constitutively and are functional in trophoblasts. However, CIITA expression was absent in trophoblasts and could not be induced by IFN-gamma. Transfection of CIITA into trophoblast 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 that bind class II promoters, nor by a lesion in the IFN-gamma signaling pathway, but results from a specific inhibition of the CIITA gene.
Morris
A C
AC
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Riley
J L
JL
Fleming
W H
WH
Boss
J M
JM
D002460:Cell Line; D005260:Female; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D005802:Genes, MHC Class II; D006801:Humans; D007108:Immune Tolerance; D050832:Interferon-Stimulated Gene Factor 3; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D009687:Nuclear Proteins; D011247:Pregnancy; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014327:Trophoblasts / Q000276:immunology / Q000378:metabolism*
D050832:Interferon-Stimulated Gene Factor 3; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; C079868:gamma interferon activation factor; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2