       Document 0075
 DOCN  M9590075
 TI    T-helper 1-type immunity to trophoblast in women with recurrent
       spontaneous abortion [see comments]
 DT    9509
 AU    Hill JA; Polgar K; Anderson DJ; Fearing Research Laboratory, Brigham and
       Women's Hospital,; Harvard Medical School, Boston, Mass 02115, USA.
 SO    JAMA. 1995 Jun 28;273(24):1933-6. Unique Identifier : AIDSLINE
       MED/95302602
 CM    Comment in: JAMA 1995 Jun 28;273(24):1958-9
 AB    OBJECTIVE--To test the hypothesis that peripheral blood mononuclear
       cells in women with unexplained recurrent abortion (URA) produce
       T-helper 1 (TH1)-type cytokines in response to trophoblast antigens.
       DESIGN--Cohort study. SETTING--Medical center. PARTICIPANTS--A total of
       244 women with URA, 13 reproductively normal parous control women, and
       10 men. MAIN OUTCOME MEASURES--Supernatants from trophoblast-activated
       peripheral blood mononuclear cells from all participants were tested for
       toxic effects on mouse embryos and by enzyme-linked immunosorbent assay
       (ELISA) for interferon gamma (IFN-gamma). Supernatants from 20 URA
       patients with embryotoxic activity and IFN-gamma, 13 reproductively
       normal parous women, and 10 men were further tested by ELISA for other
       TH1-type cytokines (interleukin-2 [IL-2], tumor necrosis factor-beta
       [TNF-beta]), TH2-type cytokines (IL-4, IL-10), and TNF-alpha.
       RESULTS--Embryotoxic activity was detected in supernatants from 160 of
       244 URA patients and in none of the controls. Interferon gamma was
       detected in supernatants from 125 of 244 URA patients and was
       significantly associated with embryotoxicity (121 of 160 supernatants
       with embryotoxicity vs four of 84 supernatants without embryotoxicity [P
       < .001]). Of 20 supernatants from patients chosen for further study, all
       were positive for TNF-alpha, 17 for TNF-beta, two for IL-10, and one for
       IL-4. No cytokines were detected in supernatants from unstimulated or
       red blood cell membrane-activated cells of women with URA. In contrast,
       trophoblast-activated lymphocyte supernatants from reproductively normal
       women and men neither were embryotoxic nor contained TH1-type cytokines,
       but most contained the TH2-type cytokine IL-10. Three supernatants from
       reproductively normal women also contained IL-4. CONCLUSION--Whereas
       TH1-type immunity to trophoblast is associated with URA and may play a
       role in reproductive failure, TH2-type immunity may be a natural
       response to trophoblast contributing to successful pregnancy.
 DE    Abortion, Habitual/*IMMUNOLOGY  Adult  Animal  Cohort Studies
       Comparative Study  Cytokines/BLOOD/*SECRETION/*TOXICITY  Embryo/DRUG
       EFFECTS  Female  Human  Interferon Type II/BLOOD/SECRETION  Male  Mice
       Pregnancy/*IMMUNOLOGY  Support, Non-U.S. Gov't  Support, U.S. Gov't,
       P.H.S.  Th1 Cells/*PHYSIOLOGY/SECRETION  Th2 Cells/PHYSIOLOGY
       Trophoblast/IMMUNOLOGY/*PHYSIOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

