Adenovirus mediated CTLA4Ig transgene therapy alleviates abortion by inhibiting spleen lymphocyte proliferation and regulating apoptosis in the feto-placental unit

Pregnancy is thought to be a state of immunological tolerance. The mechanisms underlying this phenomenon are still poorly understood. In our previous study, adenovirus mediated CTLA4Ig transgene (Ad-CTLA4Ig) therapy was demonstrated to improve pregnancy outcome in an abortion-prone mouse model by skewing the Th2/Th1 cytokine balance, expanding peripheral CD4+ CD25+ regulatory T cell populations and inducing indoleamine 2,3 dioxygenase (IDO) mRNA expression at the maternal–fetal interface. However, it is still not clear whether other mechanisms are involved in the protective effect of CTLA-4 on pregnancy outcome in abortion-prone matings. In this study, we focused on the effect of CTLA4Ig on spleen lymphocyte proliferation and apoptosis at the maternal–fetal interface. We demonstrated that Ad-CTLA4Ig therapy inhibited the proliferation of CBA/J splenocytes and IL-2 secretion in response to DBA/2 stimulator cells in the abortion-prone mice model. Ad-CTLA4Ig therapy also skewed cytokine production toward a Th2 bias and regulated the expression of anti-apoptosis factor Bcl-2 and pro-apoptosis factor Bax at the maternal–fetal interface. However, it did not influence the apoptosis and cell cycles of splenocytes in pregnant CBA/J mice. On the whole, these findings indicated that Ad-CTLA4Ig therapy could ameliorate the outcome of spontaneous abortion by inhibiting proliferation of maternal spleen lymphocytes and regulating apoptosis in the feto-placental unit.