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. 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.
|Keywords||T-cell reactivity, paternal antigens, preeclampsia, pregnancy|
|Persistent URL||dx.doi.org/10.1016/j.ajog.2010.06.047, hdl.handle.net/1765/20998|
|Note||Article in press - dd Oktober 2010|
de Groot, C.J.M., van der Mast, B.J., Visser, W., Kuiper, P., Weimar, W., & van Besouw, N.M.. (2010). Preeclampsia is associated with increased cytotoxic T-cell capacity to paternal antigens. American Journal of Obstetrics & Gynecology, 203(5), 1–6. doi:10.1016/j.ajog.2010.06.047