Blockade of CD80 and CD86 at the time of implantation inhibits maternal rejection to the allogeneic fetus in abortion-prone matings.
CD28/CTLA-4 interactions with their specific B7-ligands (CD80 and CD86) play a decisive role in antigenic and allogenic responses. Recently, experimental transplant studies demonstrated that donor-specific tolerance was achieved by blocking these interactions. However, the role of blockade of CD28/B7 costimulatory pathway in the maintenance of materno-fetal tolerance has received little attention. In the present study, abortion-prone CBA/J females mated with DBA/2 males were administered with anti-CD80 and anti-CD86 monoclonal antibodies (mAbs) on day 4 of gestation (time of murine implantation). We demonstrated that the combined use of anti-CD80 and anti-CD86 mAbs induced maternal tolerance to the fetus in the abortion-prone CBA/J mice, and displayed expansion of the maternal CD4(+)CD25+ regulatory T cell population and up-regulated expression of CTLA-4, suggesting an active mechanism of regulatory T cells in suppressing maternal rejection to the fetus. In addition, the anti-CD80/86 mAbs treatment enhanced Th2 and reduced Th1 cytokine production in mice, implying that the development of Th2 cells might contribute to maternal tolerance to her fetus. Together, these findings indicated that blocking CD80 and CD86 enhanced maternal tolerance to her fetus in mice by increasing regulatory T cell function and skewing toward a Th2 response. Our data might provide an enhanced understanding of the maternal-fetal immune relationship and be helpful in clinical trials for immunotherapy of recurrent spontaneous abortion.
Jin
Li-Ping
LP
Laboratory for Reproductive Immunology, Institute of Obstetrics and Gynecology, Fudan University, 419 Fangxie Road, Shanghai 200011, China.
Zhou
Yue-Hua
YH
Wang
Ming-Yan
MY
Zhu
Xiao-Yong
XY
Li
Da-Jin
DJ
D000022:Abortion, Spontaneous / Q000276:immunology* / Q000517:prevention & control; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen; D005260:Female; D007108:Immune Tolerance; D007274:Injections, Intraperitoneal; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D051379:Mice; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000276:immunology; D012098:Reproduction / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins