Preeclampsia is associated with increased cytotoxic T-cell capacity to paternal antigens.
OBJECTIVE
During an uncomplicated pregnancy the conceptus is a semiallogeneic entity in which rejection is prevented by suppression of the maternal immune system. We hypothesized that this suppression is disturbed in patients with preeclampsia and that a maternal immune response to fetal (foreign/paternal) antigens in the fetal-maternal interface may be responsible for local inflammation, with subsequent endothelial dysfunction and systemic disease.


METHODS
Blood samples were obtained from 14 women with preeclampsia (cases), 14 gestational-age and parity-matched women with uncomplicated pregnancies (controls), and their partners. We determined the partner-specific cytotoxic T-lymphocyte precursor frequency (CTLpf) and the CTLpf directed to unrelated partners with uncomplicated pregnancies. We measured the CTLpf in peripheral blood mononuclear cells (PBMCs) from cases and controls using limited-dilution assays. In addition, proliferation was tested in a mixed-lymphocyte culture (MLR).


RESULTS
The partner-specific CTLpf was significantly higher in cases compared with controls (median, 183 [15-338] vs 67 [9-232] per million PBMCs, P = .02). In contrast, in women with uncomplicated pregnancies, the partner-specific CTLpf was down-regulated compared with the CTLpf directed to an unrelated partner who fathered uncomplicated pregnancies (P = .02). No difference was found in partner-specific MLR response between cases and controls.


CONCLUSIONS
These results suggest that women with preeclampsia have a higher cytotoxic T-cell response to paternal antigens compared with pregnant controls. This insufficiently suppressed immune response may eventually lead to the development of preeclampsia.
de Groot
Christianne J M
CJ
Department of Obstetrics and Gynecology, Erasmus University Medical Center, Rotterdam, The Netherlands. cdegroot@me.com
van der Mast
Barbara J
BJ
Visser
Willy
W
De Kuiper
Petronella
P
Weimar
Willem
W
Van Besouw
Nicole M
NM
D000328:Adult; D000941:Antigens / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D011225:Pre-Eclampsia / Q000276:immunology*; D011247:Pregnancy; D018709:Statistics, Nonparametric; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*
D000941:Antigens