Constitutive intracellular expression of human leukocyte antigen (HLA)-DO and HLA-DR but not HLA-DM in trophoblast cells.
The nonclassic human leukocyte antigen (HLA)-DM molecules have been proved to positively regulate antigen presentation in classic antigen-presenting cells, whereas in B lymphocytes HLA-DO have been identified as negative regulators of the process. The present report examines whether the negative expression of classic class II molecules in trophoblasts implies negative regulation by HLA-DO. It was revealed by immunofluorescence, confocal microscopy, and subcellular fractionation techniques that human trophoblasts, although not expressing any surface HLA-DR antigens, constitutively express intracellular HLA-DR, HLA-DO, and CD74, but not HLA-DM. Administration of interferon-gamma to the cell culture increased HLA-DR and CD74, induced HLA-DM, but did not alter the expression of HLA-DO and induced HLA-DR release from the cells. These results were confirmed by reverse transcriptase-polymerase chain reaction analysis except that HLA-DM mRNA was detected in control cells, indicating a posttranscriptional regulation. Under the same experimental conditions, human monocytes/macrophages were not expressing intracellular HLA-DO while exhibiting significant levels of HLA-DR, HLA-DM, and CD74. The results presented here reveal for the first time expression of HLA-DO in trophoblasts, which can be of great importance in maintaining the class II-negative state in these cells and consequently protecting the fetus from maternal immune attack.
Ranella
Anthi
A
Department of Biology, Laboratory of Immunology, University of Crete, Heraklion, Crete, Greece.
Vassiliadis
Simon
S
Mastora
Chrisa
C
Valentina
Michailidou
M
Dionyssopoulou
Eva
E
Athanassakis
Irene
I
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000276:immunology*; D003593:Cytoplasm / Q000276:immunology; D005260:Female; D005455:Fluorescent Antibody Technique; D006681:HLA-D Antigens / Q000096:biosynthesis / Q000276:immunology*; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D011994:Recombinant Proteins; D014327:Trophoblasts / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D000944:Antigens, Differentiation, B-Lymphocyte; D006681:HLA-D Antigens; C084245:HLA-DM antigens; C046148:HLA-DO antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D011994:Recombinant Proteins; C045084:invariant chain; D007371:Interferon-gamma