ヤマザキ　ケンジ   KENJI YAMAZAKI   山崎　健二    所属   医学部 医学科（東京女子医科大学病院）    職種   客員教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Donor bone marrow cells are essential for iNKT cell-mediated Foxp3+ Treg cell expansion in a murine model of transplantation tolerance.
掲載誌名	正式名：European journal of immunology 略　 称：Eur J Immunol ISSNコード：00142980/15214141
掲載区分	国外
出版社	John Wiley & Sons, Inc.
巻・号・頁	47(4),pp.734-742
著者・共著者	MIYAIRI Satoshi†, HIRAI Toshihito*, ISHII Rumi, OKUMI Masayoshi, NUNODA Shinichi, YAMAZAKI Kenji, ISHII Yasuyuki, TANABE Kazunari
発行年月	2017/04
概要	Mixed chimerism induction is the most reliable method for establishing transplantation tolerance. We previously described a novel treatment using a suboptimal dose of anti-CD40 ligand (anti-CD40L) and liposomal formulation of a ligand for invariant natural killer T cells administered to sub-lethally irradiated recipient mice after donor bone marrow cell (BMC) transfer. Recipient mice treated with this regimen showed expansion of a Foxp3-positive regulatory T(Treg) cell phenotype, and formation of mixed chimera. However, the mechanism of expansion and bioactivity of Treg cells remains unclear. Here, we examine the role of donor BMCs in the expansion of bioactive Treg cells. The mouse model was transplanted with a heart allograft the day after treatment. The results showed that transfer of spleen cells in place of BMCs failed to deplete host interferon (IFN)-γ-producing CD8+T cells, expand host Ki67+CD4+CD25+Foxp3+ Treg cells, and prolong graft survival. Severe combined immunodeficiency mice who received Treg cells obtained from BMC-recipients accepted skin grafts in an allo-specific manner. Myeloid-derived suppressor cells, which were a copious cell subset in BMCs, enhanced the Ki67 expression of Treg cells. This suggests that donor BMCs are indispensable for the expansion of host bioactive Treg cells in our novel treatment for transplant tolerance induction.
DOI	10.1002/eji.201646670
PMID	28127757