| Project/Area Number |
16590954
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
SHIMAZAKI Chihiro Kyoto Prefectural University of Medicine, Deprtment of Medicine, assistant Professor, 医学研究科, 講師 (50170931)
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| Co-Investigator(Kenkyū-buntansha) |
AKATSUKA Yoshiki Aichi Cancer Center, Department of Tiumor Immunology, Head Reseacher, 腫瘍免疫学部, 主任研究員 (70333391)
丸屋 悦子 特定非営利活動法人HLA研究所, 主任研究員
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | feto-maternal immun tolerance / feto-matemal microchimerism / ELISPOT assay / haploidentical transplantation / allogeneic stem cell transplantation / 母児間マイクロキメリズム / ELISPOTアッセィ |
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| Research Abstract |
Reciprocal cell traffic between mother and fetus during pregnancy gives rise to postpartum fetal-maternal lymphohematopoietic microchimerism, which is frequently detected in blood and tissue from healthy individuals. Recent clinical experiences have suggested the association of microchimerism with acquired immunologic hyporesponsiveness to non-inherited maternal HLA antigens (NIMA) or inherited paternal HLA antigens (IPA). Based on these hypothesis we have started a non-T cell-depleted HLA haploidentical stem cell transplantation between mother and child or between NIMA-mismatched siblings. This study demonstrated a relatively low incidence of severe graft-versus-host disease (GVHD). However, no methods have been established to detect immune hyporesponsiveness to NIMA or IPA in vitro. In the present study, we developed a new method to detect the in vitro T cell reactivity of healthy individuals toward NIMA or IPA using interferon-γ (IFN-γ) Elispot analysis. CD3+ T cell reactivity from healthy individuals is very low toward autologous antigen presenting cells (CD19+ B cells), and is higher toward antigen presenting cells from the third party. CD3+ T cell reactivity toward NIMA is lower than that from the third party, but higher than autologous antigen presenting cells. In addition, CD3+ T cell reactivity toward IPA is similar to that from the third party. These observations suggest that this method using IFN-γ Elispot assay might be useful to speculate the immune tolerance toward NIMA and IPA, and predict GVHD after haploidentical stem cell transplantation between NIMA/IPA-mismatched family members.
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