胎盤衍生的可溶性MICA/B在懷孕血清中的變化及羊水對活化的單核性細胞產生TH1/TH2細胞激素的影響

Abstract

The survival of the semi-allogeneic fetus which can escape from the maternal immune attack during human normal pregnancy is a special immunological phenomenon. Several hypothetical mechanisms are proposed to explain these particular modifications of the immune status of the mother. Lucia Mincheva-Nilsson et al. (2006) suggested a new physiological mechanism for fetal evasion from maternal immune attack in that the engagement and down-regulation of the NK cell receptor NKG2D by soluble MHC class I chain-related proteins (sMIC) A and B derived from placenta occurred in the mother side. Following this report, we hypothesized that the sMICA/B level would increase in proportion to the gestational age for protecting the fetus from maternal immune rejection in the normal pregnancy. In the present study, we collected 337 serum specimens from 290 normal pregnancy women for sMICA/B analysis. We found the serum sMICA/B level rose gradually with the progression of gestation, and reached the peak value in the second trimester. The sMICA/B level decreased after the third trimester, with the lowest level appearing before delivery. According to these findings, we conclude that when approaching delivery, the aged placenta produces reduced amount of soluble MICA/B and induce the labor. In addition, we collected 10 amniotic fluid samples from the normal second-trimester pregnant women and measured the concentration of soluble MICA/B in amniotic fluid. We found the level of soluble MICA/B were extremely low in amniotic fluid. We suggest the effect of soluble MICA/B on natural killer cells of the pregnant women is limited to the placental maternal surface, but not transferring through the placenta into the amniotic cavity. In addition, we collected another 25 amniotic fluid samples from the normal second-trimester pregnant women and analyzed the influence of amniotic fluid on the TH1/TH2 cytokine production of the activated mononuclear cell. Interestingly, we demonstrated that some of the amniotic fluid suppressed IFN-γ, but not IL-10, production by anti-CD3+/anti-CD28 activated mononuclear cells. In conclusion, both pregnancy serum and amniotic fluid exhibit immno-modulatory effects on the feto-maternal inmmunotolerance.