Altered phenotype of HLA-G expressing trophoblast and decidual natural killer cells in pathological pregnancies.
BACKGROUND
The interaction between decidual natural killer (NK) cells and alloantigens expressed on fetal trophoblast cells are thought to be essential for successful implantation and placentation. Consequently, a disturbed interaction during the first trimester of pregnancy might well lead to a subsequent pregnancy failure.


METHODS
We investigated the expression of HLA-G and NK cell markers in tissue sections from recurrent miscarriage (n = 9) and ectopic tubal pregnancies (n = 5), and two hysterectomy specimens of healthy pregnancy as well as decidual biopsies (n = 9) were used as controls.


RESULTS
We show in normal pregnancy not only a decrease, but also a morphological change in CD56+ NK cells upon interaction with HLA-G-expressing trophoblasts. The cells appear to be transitioning from a blast-like (activation) state into a state of apoptosis. The number of CD16+ NK cells was low. In contrast, in recurrent miscarriage tissue a sustained NK cell marker expression of both CD56 and CD16 was paralleled by a decreased expression of HLA-G. No morphological changes from the blast-like stage were apparent. Finally, in ectopic pregnancies HLA-G expression in the absence of decidual NK cells was associated with a disturbed trophoblast differentiation.


CONCLUSIONS
In pathological pregnancies we show an in-situ altered phenotype of trophoblast and NK cells.
Emmer
Peter M
PM
Department of Blood Transfusion and Transplantation Immunology, University Medical Centre Nijmegen, 6500 HB, Nijmegen, The Netherlands.
Steegers
Eric A P
EA
Kerstens
Harold M J
HM
Bulten
Johan
J
Nelen
Willianne L D M
WL
Boer
Kees
K
Joosten
Irma
I
D000026:Abortion, Habitual / Q000235:genetics / Q000276:immunology*; D003656:Decidua / Q000276:immunology*; D005260:Female; D006680:HLA Antigens / Q000032:analysis*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology* / Q000502:physiology; D011247:Pregnancy; D011271:Pregnancy, Ectopic / Q000235:genetics / Q000276:immunology*; D012016:Reference Values; D014327:Trophoblasts / Q000276:immunology* / Q000502:physiology
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I