2004 Fiscal Year Final Research Report Summary
NK and NKT cells, Th1/Th2 cytokines in immune reproductive failure
| Project/Area Number |
14370521
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
YAMADA Hideto Hokkaido Univ., Grad.School of Med., Asso.Prof., 大学院・医学研究科, 助教授 (40220397)
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| Co-Investigator(Kenkyū-buntansha) |
MINAKAMI Hisanori Hokkaido Univ., Grad.School of Med., Prof., 大学院・医学研究科, 教授 (40102256)
FURUTA Itsuko Hokkaido Univ., Grad.School of Med., Inst., 大学院・医学研究科, 助手 (70238682)
KATAOKA Soromon Hokkaido Univ., Hokkaido Univ.Hospital, MD., 病院・医員 (50374377)
MORIKAWA Mamoru Hokkaido Univ., Hokkaido Univ.Hospital, MD., 病院・医員 (00374380)
ONOE Kazunori Hokkaido Univ., Institute for Genetic Medicine, Prof., 遺伝子病制御研究所, 教授 (40002117)
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| Project Period (FY) |
2002 – 2004
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| Keywords | Infertility / Recurrent Miscarriage / NK cell / NKT cell / Th1 cytokine / Th2 cytokine |
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| Research Abstract |
The aim of this study was to investigate pathophysiological roles of NK and NKT cells, Th1/Th2 cytokines in immune reproductive failure. We found that high NK cell activities in the circulation of women with recurrent miscarriage (RM) were associated with subsequent miscarriage with normal fetal chromosome. Decreases in KIR2DL1 (CD158a) expression on NK cells and in T cell population, Th2/Tc2-sift were found in the circulation of RM women. Frequencies of CD3+cells, CD4+IFN-g+cells, CD4+TNF-a+cells were decreased in the endometria of RM women. In a prospective study, we found decreases in CD158a, CD94, and CD244 expression on NK cells and increases in perform expression in the deciduas of sporadic cases of miscarriage with normal fetal chromosome.
Gene polymorphisms such as GST M1 null (OR2.2), CYP17 A2 allele (OR2.4), IL-6 G allele (OR0.46) were found to be associated RM risk, suggesting that RM is a polygenetic disease. We found that daily caffeine intake was associated with RM risk only in women who carried CYP1A2^* 1F homozygous A allele (100-299 mg/day OR 1.9,≧300mg/day OR 5.2), and suggested that RM is a life-style related disease.
We used poly(I:C)-induced fetal resorption prone mating of CBA/J×DBA/2J mice. Injections of intact type human Ig and mouse Ig significantly reduced fetal resorption rates from 55% to 8.5% and 0%, respectively. But this anti-miscarriage effect was not detected by injections of Fab fragments of human Ig. We performed a variety of adoptive transfer experiments in which spleen cells from Ig-injected donors were transferred to poly(I:C)-injected pregnant recipients. Adoptive transfer of spleen cells with enrichment of macrophages retained the anti-miscarriage effect. However, this anti-miscarriage effect completely disappeared, if macrophages were depleted from transferred spleen cells. It was for the first time demonstrated that Ig-stimulated macrophages carried the anti-miscarriage effects in which Fc portions of Ig playd a critical role.
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