Origin of Foxp3(+) cells during pregnancy.

Pregnancy establishment and maintenance represents a challenge for the maternal immune system because it has to be alert against pathogens while tolerating paternal alloantigens expressed in fetal structures. Regulatory T cells (Tregs) are important for successful implantation and involved in allotolerance towards paternal antigens. The origin and mechanisms leading to Treg generation during pregnancy at different stages remain under discussion.

Blockage of heme oxygenase-1 abrogates the protective effect of regulatory T cells on murine pregnancy and promotes the maturation of dendritic cells.

Regulatory T cells (Treg) play an important role in fetal protection. They expand during normal pregnancy and protect fetal antigens from maternal effector cells. Their effect is associated with the up-regulation of tolerance-associated molecules at the fetal-maternal interface.

The persistence of paternal antigens in the maternal body is involved in regulatory T-cell expansion and fetal-maternal tolerance in murine pregnancy.

Problem: Mammalian pregnancy is a state of immunological tolerance and CD4(+) CD25(+) regulatory T cells (Treg) contribute to its maintenance. Knowing that Treg act in an antigen-specific way during pregnancy, we hypothesized that they are generated after maternal immune cells encounter paternal antigens.

Method Of Study: We mated wild type females with transgenic green fluorescent protein (GFP) males in an allogenic setting and killed them on different days of pregnancy.

PD-1 but not CTLA-4 blockage abrogates the protective effect of regulatory T cells in a pregnancy murine model.

Problem: Regulatory T cells (Treg) play an important role in fetal protection. They expand during normal pregnancy and protect paternal/fetal antigens from rejection by maternal effector cells. Accordingly, the transfer of Treg obtained from BALB/c-mated CBA/J females prevents abortion in DBA/2J-mated animals.

Supporting the hypothesis of pregnancy as a tumor: survivin is upregulated in normal pregnant mice and participates in human trophoblast proliferation.

Problem: Survivin, a tumor-promoting antiapoptotic molecule, is expressed in the human placenta. Here, we analyzed its expression during normal and pathological murine pregnancy and investigated its participation in human first trimester trophoblast cell survival and proliferation.

Method Of Study: We first analyzed the expression of survivin on the mRNA and protein level at the fetal-maternal interface of normal pregnant (CBA/J x BALB/c) and abortion-prone (CBA/J x DBA/2J) mice at different pregnancy stages by RT-PCR and immunohistochemistry.

Mechanisms of action of regulatory T cells specific for paternal antigens during pregnancy.

Objective: To investigate whether pregnancy-induced regulatory T cells are generated specifically for paternal antigens or expanded by hormonal changes and to study regulatory T cell-related mechanisms during pregnancy.

Methods: We used murine models of normal, abortion-prone, and pseudopregnancy to characterize regulatory T cells and hormones by methods such as flow cytometry, molecular biology techniques, and chemiluminescence. Antigen specificity was studied in experiments in which animals were vaccinated with paternal antigens or adoptively transferred with regulatory T cells.

Development of a chitinase and v-cathepsin negative bacmid for improved integrity of secreted recombinant proteins.

The application of the baculovirus-insect cell expression system for the production of integral membrane and secreted proteins is often more troublesome than for cytoplasmic proteins. One protein expressed at low levels in insect cells is the Theileria parva sporozoite surface protein p67. Theileria parva is a protozoan parasite, which causes the tick-transmitted disease East Coast fever in cattle.