title: Differential actions of glycodelin-A on Th-1 and Th-2 cells: a paracrine mechanism that could produce the Th-2 dominant environment during pregnancy.
abstract: BACKGROUND
  The maternal-fetal interface has a unique immunological response towards the implanting placenta. It is generally accepted that a T-helper type-2 (Th-2) cytokine prevailing environment is important in pregnancy. The proportion of Th-2 cells in the peripheral blood and decidua is significantly higher in pregnant women in the first trimester than in non-pregnant women. Glycodelin-A (GdA) is a major endocrine-regulated decidual glycoprotein thought to be related to fetomaternal defence. Yet the relationship between its immunoregulatory activities and the shift towards Th-2 cytokine profile during pregnancy is unclear.
  
  
  METHODS
  GdA was immunoaffinity purified from human amniotic fluid. T-helper, T-helper type-1 (Th-1) and Th-2 cells were isolated from the peripheral blood. The viability of these cells was studied by XTT assay. Immunophenotyping of CD4/CD294, cell death and GdA-binding were determined by flow cytometry. The mRNA expression, surface expression and secretion of Fas/Fas ligand (FasL) were determined by quantitative polymerase chain reaction, flow cytometry and ELISA, respectively. The activities of caspase-3, -8 and -9 were measured. The phosphorylation of extracellular signal-regulated kinases (ERK), p38 and, c-Jun N-terminal kinase was determined by western blotting.
  
  
  RESULTS
  Although GdA bound to both Th-1 and Th-2 cells, it had differential actions on the two cell-types. GdA induced cell death of the Th-1 cells but not the Th-2 cells. The cell death was mediated through activation of caspase -3, -8 and -9 activities. GdA up-regulated the expression of Fas and inhibited ERK activation in the Th-1 cells, which might enhance the vulnerability of the cells to cell death caused by a trophoblast-derived FasL.
  
  
  CONCLUSIONS
  The data suggest that GdA could be an endometrial factor that contributes to the Th-2/Th-1 shift during pregnancy.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Hong Kong, Pokfulam Road, Hong Kong, China.
authors.forename: Cheuk-Lun
authors.initials: CL
authors.lastname: Lee
authors.forename: Philip C N
authors.initials: PC
authors.lastname: Chiu
authors.forename: Kevin K W
authors.initials: KK
authors.lastname: Lam
authors.forename: Siu-On
authors.initials: SO
authors.lastname: Siu
authors.forename: Ivan K
authors.initials: IK
authors.lastname: Chu
authors.forename: Riitta
authors.initials: R
authors.lastname: Koistinen
authors.forename: Hannu
authors.initials: H
authors.lastname: Koistinen
authors.forename: Markku
authors.initials: M
authors.lastname: Seppälä
authors.forename: Kai-Fai
authors.initials: KF
authors.lastname: Lee
authors.forename: William S B
authors.initials: WS
authors.lastname: Yeung
mesh_terms: D000653:Amniotic Fluid / Q000737:chemistry; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D054885:Cumulus Cells / Q000737:chemistry; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D000071816:Glycodelin; D006023:Glycoproteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D020033:Protein Isoforms / Q000302:isolation & purification / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012661:Semen / Q000737:chemistry; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D000071816:Glycodelin; D006023:Glycoproteins; C045246:PAEP protein, human; D011257:Pregnancy Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D019014:fas Receptor; D020169:Caspases