title: Differential immunoregulation in successful oocyte donation pregnancies compared with naturally conceived pregnancies.
abstract: In oocyte donation (OD) pregnancies, there is a higher level of antigenic dissimilarity between mother and fetus compared with naturally conceived (NC) pregnancies. We hypothesize that a higher degree and/or a different type of immunoregulation is necessary to maintain an uncomplicated OD pregnancy. Different immunological aspects of successful OD pregnancies (n=28) were compared with those of NC pregnancies (n=51), and non-donor IVF (n=20) pregnancies. Maternal peripheral blood mononuclear cells (mPBMCs) were characterized by flow cytometry; the outcome correlated with the number of mother-child HLA mismatches. The fetus-specific alloreactivity of mPBMCs was measured in a mixed lymphocyte reaction. The percentages of CD4(+)CD25(bright) and CD4(+)CD25(dim) cells were higher in mPBMCs of OD and IVF pregnancies compared with NC pregnancies. The percentage of CD4(+)CD25(dim) cells in mPBMCs of OD pregnancies correlated positively with the number of HLA mismatches. Functional studies showed a lower proliferative response to umbilical cord blood by mPBMCs in OD pregnancies. In conclusion, we found a higher degree of peripheral immunoregulation in OD and IVF pregnancies compared with NC pregnancies. A higher number of HLA mismatches in successful OD pregnancies leads to increased percentages of activated T cells in peripheral blood, but not to a higher alloreactivity to the fetus. These studies show that immunoregulation in OD pregnancy is different from that in NC pregnancies. The antigenic dissimilarity in OD pregnancies may play a role in the pathophysiology of preeclampsia.
authors.affiliation: Department of Obstetrics, Leiden University Medical Center, P.O. Box 9600 (location code: K6-26), 2300 RC Leiden, The Netherlands. Electronic address: m.l.p.van_der_hoorn@lumc.nl.
authors.forename: Marie-Louise P
authors.initials: MP
authors.lastname: van der Hoorn
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Angela
authors.initials: A
authors.lastname: van Egmond
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Godelieve M J S
authors.initials: GMJS
authors.lastname: Swings
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Els
authors.initials: E
authors.lastname: van Beelen
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Carin
authors.initials: C
authors.lastname: van der Keur
authors.affiliation: Charité Centrum 12 for Internal Medicine and Dermatology, Laboratory of Reproductive Medicine, University Medicine of Berlin, Campus Virchow Klinikum, Berlin, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Tirado-González
authors.affiliation: Charité Centrum 12 for Internal Medicine and Dermatology, Laboratory of Reproductive Medicine, University Medicine of Berlin, Campus Virchow Klinikum, Berlin, Germany.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Blois
authors.affiliation: Center for Vascular Biology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
authors.forename: S Ananth
authors.initials: SA
authors.lastname: Karumanchi
authors.affiliation: Mother Infant Research Institute at Tufts Medical Center, Boston, MA, USA.
authors.forename: Diana W
authors.initials: DW
authors.lastname: Bianchi
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Frans H J
authors.initials: FHJ
authors.lastname: Claas
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands; Department of Obstetrics and Gynecology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Sicco A
authors.initials: SA
authors.lastname: Scherjon
mesh_terms: D000328:Adult; D015704:CD4 Antigens / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D054502:Histocompatibility, Maternal-Fetal / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D056747:Immunomodulation; D016130:Immunophenotyping; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008875:Middle Aged; D018587:Oocyte Donation; D009865:Oocytes / Q000276:immunology*; D011247:Pregnancy / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D006680:HLA Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D007519:Isoantigens
keywords: Human; Immunology; In vitro fertilization; Oocyte donor; Pregnancy; Reproductive immunology; T cells; Transplantation