title: Adenovirus mediated CTLA4Ig transgene therapy alleviates abortion by inhibiting spleen lymphocyte proliferation and regulating apoptosis in the feto-placental unit.
abstract: 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.
authors: Assisted Reproductive Center, The First affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors: Weihong
authors: W
authors: Li
authors: Bin
authors: B
authors: Li
authors: Shangwei
authors: S
authors: Li
mesh_terms: D000069594:Abatacept; D000022:Abortion, Spontaneous / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D016207:Cytokines; D005260:Female; D018796:Immunoconjugates / Q000235:genetics* / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D010920:Placenta / Q000276:immunology / Q000378:metabolism; D011247:Pregnancy; D011256:Pregnancy Outcome; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007376:Interleukin-2; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D000069594:Abatacept