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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.

journal_name

J Reprod Immunol

journal_title

Journal of reproductive immunology

authors

Li W,Li B,Li S

doi

10.1016/j.jri.2013.01.002

subject

Has Abstract

pub_date

2013-04-01 00:00:00

pages

167-74

issue

2

eissn

0165-0378

issn

1872-7603

pii

S0165-0378(13)00011-9

journal_volume

97

pub_type

杂志文章

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