國家衛生研究院 NHRI:Item 3990099045/3161
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    題名: Prenatal tolerance induction: relationship between cell dose, marrow T-cells, chimerism, and tolerance
    作者: Chen, JC;Chang, ML;Huang, SF;Chang, PY;Muench, MO;Fuj, RH;Ou, LS;Kuo, ML
    貢獻者: Division of Molecular and Genomic Medicine
    摘要: It was reported that the dose of self-antigens can determine the consequence of deletional tolerance and donor T cells are critical for tolerance induction in mixed chimeras. This study aimed at assessing the effect of cell doses and marrow T cells on engraftment and tolerance induction after prenatal bone marrow transplantation. Intraperitoneal cell transplantation was performed in FVB/N (H-2Kq) mice at gestational day 14 with escalating doses of adult C57BL/6 (H-2K11) marrows. Peripheral chimerism was examined postnatally by flow cytometry and tolerance was tested by skin transplantation. Transplantation of light-density marrow cells showed a dose response. High-level chimerism emerged with a threshold dose of 5.0 x 101 and host leukocytes could be nearly replaced at a dose of 7.5-10.0 x 106. High-dose transplants conferred a steady long-lasting donor-specific tolerance but were accompanied by >50% incidence of graft- versus-host disease. Depletion of marrow T cells lessened graft-vers us- host disease to the detriment of engraftment. With low-level chimerism, tolerance was a graded phenomenon dependent upon the level of chimerism. Durable chimerism within 6 months required a threshold of ! 2% chimerism at I month of age and predicted a 50% chance of long-term tolerance, whereas transient chimerism (<2%) only caused hyporesponsiveness to the donor. Tolerance induction did not succeed without peripheral chimerism even if a large amount of injected donor cells persisted in the peritoneum. Neither did an increase in cell doses or donor T-cell contents benefit skin graft survivals unless it had substantially improved peripheral chimerism. Thus, peripheral chimerism level can be a simple and straightforward test to predict the degree of prenatal immune tolerance.
    關鍵詞: Cell Biology;Transplantation
    日期: 2008
    關聯: Cell Transplantation. 2008;17(5):495-506.
    Link to: http://www.ingentaconnect.com/content/cog/ct/2008/00000017/00000005/art00002
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0963-6897&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000258123100002
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=51749118730
    顯示於類別:[黃秀芬] 期刊論文

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