title: An imbalance in interleukin-17-producing T and Foxp3⁺ regulatory T cells in women with idiopathic recurrent pregnancy loss.
abstract: BACKGROUND
  T cells which produce interleukin (IL)-17 are involved in chronic inflammatory processes and regulatory T (Treg) cells are possibly the most important immune regulators. We aimed to investigate peripheral blood IL-17(+) T and Foxp3(+) Treg cells in women with idiopathic recurrent pregnancy loss (RPL).
  
  
  METHODS
  The study design is a cross-sectional evaluation of Th1, Th2, IL-17(+) T and Treg cells in women with idiopathic RPL (n = 42) and age-matched parous controls (n = 24). Flow cytometric analysis was performed to measure IL-17(+) T and Foxp3(+) Treg cells, and ratios of Th1/Th2 cells using anti-IL-17A and anti-Foxp3 antibodies, and monoclonal antibodies to tumor necrosis factor (TNF)-α, interferon (IFN)-γ and IL-10. Student's t-test and partial correlations were applied for statistical analysis.
  
  
  RESULTS
  TNF-α-/IL-10-producing CD3(+)CD4(+) T cell ratio was higher in women with RPL than controls (P = 0.048). Levels of IL-17(+) T cells (P = 0.021) and the IL-17(+) T/CD4(+)Foxp3(+) Treg cell ratio (P = 0.001) were increased, whereas Foxp3(+) (P = 0.035), Foxp3(low) (P = 0.032) and CD4(+)Foxp3(+) T cell (P = 0.037) levels were decreased in women with RPL, compared with controls. Levels of IL-17(+) T cells were correlated with TNF-α-producing CD3(+)CD4(+) T cells (r = 0.269, P = 0.033), and with ratios of TNF-α/IL-10 (r = 0.276, P = 0.027) and IFN-γ/IL-10 (r = 0.266, P = 0.035)-producing CD3(+)CD4(+) cells. Furthermore, the ratio of IL-17(+) T cells to CD4(+)Foxp3(+) Treg cells showed a positive correlation with TNF-α-producing CD3(+)CD4(+) T cells (P = 0.047) and IFN-γ-producing CD3(+)CD4(+) T cells (P = 0.048) as well as a ratio of IFN-γ/IL-10-producing CD3(+)CD4(+) T cells (P = 0.037).
  
  
  CONCLUSIONS
  Enhanced pro-inflammatory immune responses with suppressed immune regulation may be an important immune mechanism involved in RPL.
authors.affiliation: Department of Obstetrics and Gynecology,  College of Medicine, Konyang University, Gasoowon-dong, Seo-gu, Daejeon 302-718,  Korea.
authors.forename: S K
authors.initials: SK
authors.lastname: Lee
authors.forename: J Y
authors.initials: JY
authors.lastname: Kim
authors.forename: S E
authors.initials: SE
authors.lastname: Hur
authors.forename: C J
authors.initials: CJ
authors.lastname: Kim
authors.forename: B J
authors.initials: BJ
authors.lastname: Na
authors.forename: M
authors.initials: M
authors.lastname: Lee
authors.forename: A
authors.initials: A
authors.lastname: Gilman-Sachs
authors.forename: J
authors.initials: J
authors.lastname: Kwak-Kim
mesh_terms: D000026:Abortion, Habitual / Q000097:blood*; D000328:Adult; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D006801:Humans; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma