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

The Alteration of Placental-Derived Soluble MHC Class I Chain-Related Protein A and B during Pregnancy and the Influence of Amniotic Fluid on Activated Mononuclear Cell TH1/TH2 Cytokine Production

黃詩穎(Shih-Yin Huang)

指導教授 ： 余家利

國立臺灣大學/醫學院/分子醫學研究所/碩士(2009年)

https://doi.org/10.6342/NTU.2009.02401

摘要

胎兒對母體而言是一種半同種異體移植物，在懷孕過程中不會遭受到母體的排斥是一種很特別的免疫現象。有許多免疫學上的假說，針對這個現象提出各種免疫逃脫機制的理論。Lucia Mincheva-Nilsson et al.在2006年提出一個新的胎兒對母體免疫反應的逃脫機制：人類的胎盤會分泌可溶性的MICA/B，它會與母體自然殺手細胞上的NKG2D受體結合，進而調節降低細胞的毒殺活性。根據這項研究推測：正常懷孕的婦女，隨著妊娠的進展及胎兒的成長，為保護胎兒不受母體的免疫細胞攻擊，母體血液中的可溶性MICA/B值應該會隨著妊娠週數增加。因此，本次研究收集了290位懷孕婦女的血清，分前、中、及後三個妊娠期，抽取母體周邊血液共337管，以ELISA分析可溶性MICA/B在正常妊娠期的變化。結果顯示：可溶性MICA/B在懷孕初期會隨著妊娠進展而增加，在孕程中期達到最高，但在接近生產時會下降，甚至低於孕程前期。針對此項發現我們進一步提出假設：在接近生產時，因胎盤功能的老化，使得胎盤分泌可溶性的MICA/B的能力降低所致，因此母體內可偵測到的可溶性MICA/B也相對下降。同時我們推論這可能也是誘發產程的機轉之一。另外，本次研究收集35位懷孕中期婦女的羊水，偵測其羊水中MICA/B的濃度及羊水對單核球產生IFN-γ及IL-10的影響。研究結果顯示：羊水內MICA/B的含量極低，但是我們發現有些羊水會抑制活化單核球產生IFN-γ，但不影響IL-10的產生。因此我們推論MICA/B與NKG2D的反應只局限於母體與胎盤間，並未穿過胎盤到達羊膜腔內，而羊水含有某些會抑制細胞性免疫功能的分子，其特性正在探討中

關鍵字

可溶性MICA/B ； 免疫逃脫機制 ； 懷孕 ； 羊水 ； IFN-γ

並列摘要

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.

並列關鍵字

sMICA/B ； immune evasion ； pregnancy ； amniotic fluid ； IFN-γ

參考文獻

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