van den Elsen P J, van der Stoep N, Viëtor H E, Wilson L, van Zutphen M, Gobin S J
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Hum Immunol. 2000 Sep;61(9):850-62. doi: 10.1016/s0198-8859(00)00159-2.
Lack of MHC-mediated antigen presenting functions of fetal trophoblast cells is an important mechanism to evade maternal immune recognition. In this study we demonstrated that the deficiency in MHC expression and antigen presentation in the trophoblast cell lines JEG-3 and JAR is caused by lack of class II transactivator (CIITA) expression due to hypermethylation of its interferon-gamma (IFN-gamma)-responsive promoter (PIV). Circumvention of this lack of CIITA expression by introduction of exogenous CIITA induced cell surface expression of HLA-DR, -DP, and -DQ, leading to an acquired capacity to present antigen to antigen-specific T cells. Transfection of CIITA in JEG-3 cells also upregulated functional HLA-B and HLA-C expression. Noteworthy, this lack of IFN-gamma-mediated induction of CIITA was also found to exist in normal trophoblast cells expanded from chorionic villus biopsies. Together, these observations demonstrate that lack of CIITA expression is central to the absence of antigen presentation functions of trophoblast cells.
胎儿滋养层细胞缺乏MHC介导的抗原呈递功能是逃避母体免疫识别的重要机制。在本研究中，我们证明了滋养层细胞系JEG-3和JAR中MHC表达及抗原呈递的缺陷是由于其干扰素-γ（IFN-γ）反应性启动子（PIV）的高甲基化导致II类反式激活因子（CIITA）表达缺失所致。通过引入外源性CIITA来克服这种CIITA表达的缺失，可诱导HLA-DR、-DP和-DQ在细胞表面的表达，从而获得将抗原呈递给抗原特异性T细胞的能力。在JEG-3细胞中转入CIITA也会上调功能性HLA-B和HLA-C的表达。值得注意的是，从绒毛膜绒毛活检中扩增出的正常滋养层细胞中也存在这种IFN-γ介导的CIITA诱导缺失。总之，这些观察结果表明，CIITA表达的缺失是滋养层细胞缺乏抗原呈递功能的核心所在。
