1993 Fiscal Year Final Research Report Summary
Investigation of Systemic and Local Immune-mechanism for Maintenance of Human Pregnancy
| Project/Area Number |
04454425
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Keio University |
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Principal Investigator |
MAKINO Tsunehisa keio University, School of Medicine, Assistant Professor, 医学部, 講師 (30085758)
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| Co-Investigator(Kenkyū-buntansha) |
細川 知俊 慶應義塾大学, 医学部, 助手 (10238751)
染谷 健一 慶應義塾大学, 医学部, 助手 (90236159)
OZAWA Nobuaki Keio University, School of Medicine, Clinical fellow, 医学部, 助手 (70224219)
MATSUBAYASHI Hidehiko Keio University, School of Medicine, Clininal fellow, 医学部, 助手 (40219465)
MARUYAMA Tetsuo Keio University, School of Medicine, Clinical fellow, 医学部, 助手 (10209702)
IWASAKI Ken-ichi Keio University, School of Medicine, Clininal fellow, 医学部, 助手 (00203365)
SUGI Toshitaka Keio University, School of Medicine, Clinical fellow, 医学部, 助手 (70196707)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Habitual abortion / Immunotherapy / Flow cytometry / Flow cytometric crossmatch / Activated T cell / Natulal killer cell / Blocking antibody / Decidua |
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| Research Abstract |
First 1,520 couples with a history of recurrent spontaneous abortion were registered, then possible etiologic factors of the reproductive wastage were screened through comprehensive clinical examinations. Among these patienats, 214 congenial uterine malfomations, 106 chromosomal abnormalities in either husbands or wives, 24 antiphospholipid syndromes were detected. Other 482 couples were then the subjects whether they have any immunologic abnormalities in terms of maintenance of pregnancy.
Immunotherapy was performed in 473 female partners using paternal lymphocytes, resulting 77.7% of successful rate of maintenance of pregnancy. Mixed lymphocyte reaction (MLR) was significantly (p<0.001) inhibited after immunotherapy. The mean inhibition rate was 50.2%, indicating the MLR blocking antibodies were induced. It was also suggested that anti-idiotypic antibodies were gererated by immunotherapy. The percentage of cytotoxic T cell was significantly decreased (p<0.05) and that of suppressor T
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cell was significantly increased (p<0.01) after immunization, suggesting that a cell-mediated immune response was induced by immunotherapy. Two-color T cell flow cytometric crossmatch (T-FCXM) which can detect maternal IgG antibodies against paternal T lymphocytes predicts subsequent pregnancy outcome in patients undergoing immunotherapy. Anti-fetal lymphocyte antibodies were detected in only limited cases of immunized patients, suggesting that this antibody is not essential for the maintenance of pregnancy.
Flow cytometry was also used to characterize immune cell populations in the decidua to demonstrate how the proportions of immunocompetent cell populations at the feto-maternal interface are influenced by the presence and state of a feto-placental allograft. The percentage of decidual CD3^+/HLA DR^+ cells, which are characteristic of activated T cells, was significantly higher in spontaneous abortion than in normal pregnancy (p<0.05), suggesting that on/off-switching of activation of decidual T cells may be associated with maintenance of gestation.
All these studies summarized that multiple pathways of both systemic and local immune-system are essentical for the successful course of human pregnancy. Less
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