Preeclampsia is associated with increased cytotoxic T-cell capacity to paternal antigens

• Published in: American journal of obstetrics and gynecology Vol. 203; no. 5; pp. 496.e1 - 496.e6
• Main Authors: de Groot, Christianne J.M., MD, PhD, van der Mast, Barbara J., PhD, Visser, Willy, MD, PhD, De Kuiper, Petronella, BSc, Weimar, Willem, MD, PhD, Van Besouw, Nicole M., PhD
• Format: Journal Article
• Language: English
• Published: United States Mosby, Inc 01-11-2010
• Subjects: Adult; Antigens - immunology; Cells, Cultured; Female; Humans; Lymphocyte Culture Test, Mixed; Male; Obstetrics and Gynecology; paternal antigens; Pre-Eclampsia - immunology; preeclampsia; Pregnancy; Statistics, Nonparametric; T-cell reactivity; T-Lymphocytes, Cytotoxic - cytology; T-Lymphocytes, Cytotoxic - immunology; preeclampsia; T-cell reactivity; paternal antigens; pregnancy
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2010.06.047

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. Study Design 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. Conclusion 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.