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MHC Class II Gene Silencing in Trophoblast Cells Is Caused by Inhibition of CIITA Expression
Author(s) -
MORRIS ANN C.,
RILEY JAMES L.,
FLEMING WILLIAM H.,
BOSS JEREMY M.
Publication year - 1998
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/j.1600-0897.1998.tb00423.x
Subject(s) - ciita , trophoblast , biology , mhc class ii , cd74 , major histocompatibility complex , mhc class i , microbiology and biotechnology , gene silencing , transfection , immunology , cell culture , gene , genetics , antigen , fetus , placenta , pregnancy
PROBLEM: Major histocompatibility complex (MHC) class II molecule expression is specifically suppressed on fetal trophoblasts, even in response to interferon (IFN)‐γ, 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. METHOD OF STUDY: Human trophoblast cell lines were examined for expression of MHC class II transcription factors and for activity of the IFN‐γ 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‐γ 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‐γ. 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‐γ in trophoblast cells is caused neither by the absence of factors that bind class II promoters, nor by a lesion in the IFN‐γ signaling pathway, but results from a specific inhibition of the CIITA gene.