Expansion of CD4+CD25+ regulatory T cells from cord blood CD4+ cells using the common γ-chain cytokines (IL-2 and IL-15) and rapamycin

Asanuma, Shinsuke; Tanaka, Junji; Sugita, Junichi; Kosugi, Mizuha; Shiratori, Souichi; Wakasa, Kentarou; Shono, Yusuke; Shigematsu, Akio; Kondo, Takeshi; Kobayashi, Takahiko; Asaka, Masahiro; Imamura, Masahiro

Expansion of CD4+CD25+ regulatory T cells from cord blood CD4+ cells using the common γ-chain cytokines (IL-2 and IL-15) and rapamycin

Asanuma, Shinsuke; Tanaka, Junji; Sugita, Junichi et al.

Annals of Hematology, 2011, 90(6), 617-624

Permalink : https://hdl.handle.net/2115/49334

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アクセス権	open access
URI	https://hdl.handle.net/2115/49334
タイトル	Expansion of CD4+CD25+ regulatory T cells from cord blood CD4+ cells using the common γ-chain cytokines (IL-2 and IL-15) and rapamycin
著者	Asanuma, Shinsuke ; Tanaka, Junji ; Sugita, Junichi ; Kosugi, Mizuha ; Shiratori, Souichi ; Wakasa, Kentarou ; Shono, Yusuke ; Shigematsu, Akio ; Kondo, Takeshi ; Kobayashi, Takahiko ; Asaka, Masahiro ; Imamura, Masahiro
著者名 Asanuma, Shinsuke
e-Rad_Researcher 50250452 著者名 Tanaka, Junji
著者名 Sugita, Junichi
著者名 Kosugi, Mizuha
著者名 Shiratori, Souichi
著者名 Wakasa, Kentarou
著者名 Shono, Yusuke
著者名 Shigematsu, Akio
e-Rad_Researcher 70333606 著者名 Kondo, Takeshi
e-Rad_Researcher 80333607 著者名 Kobayashi, Takahiko
e-Rad_Researcher 10113507 著者名 Asaka, Masahiro
e-Rad_Researcher 20160062 著者名 Imamura, Masahiro
言語	英語
キーワード	Regulatory T cells
	IL-2
	IL-15
	Rapamycin
	Cord blood
発行日	2011-06
出版者	Springer Berlin / Heidelberg
収録物名	Annals of Hematology
巻(号)	90(6)
ページ	617-624
抄録	Rapamycin has important roles in the modulation of regulatory T cells. We tried to expand CD4+ CD25+ regulatory T cells (Treg cells) from umbilical cord blood (CB) CD4-positive cells using IL-15 or IL-2 with TGF-β and rapamycin. We were able to obtain more than 500-fold expansion of CD4+CD25+ cells from CB CD4+ cells using IL-15 and TGF-β with rapamycin. These expanded CD4+CD25+ cells expressed FoxP3 mRNA at a level about 100-fold higher and could suppress allogeneic mixed lymphocyte culture by more than 50%. Early after rapamycin stimulation, CB CD4+ cells showed increased expression of Foxp3 and a serine/threonine kinase Pim2 and sustained expression of negative PI3K regulator PTEN. On the other hand, CD4+CD25+ cells expanded with rapamycin for 8 days showed much higher levels of FoxP3 mRNA expression and decreased expression of PTEN. A comparison of IL-15 stimulation and IL-2 stimulation showed slightly higher efficiency of IL-15 for expansion of CD4+CD25+ cells and for FoxP3 expression, IL-15 also showed significantly higher efficacy for inhibition of MLC. The combination of the common γ-chain cytokine IL-15, TGF-β and rapamycin may be a useful means for expanding Treg cells. Pim2 expression early after stimulation with rapamycin may be important for conferring rapamycin resistance for growth of Treg cells. IL-15 is not less useful than IL-2 for expansion of Treg cells.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	The original publication is available at www.springerlink.com
PISSN	0939-5555
関連情報	PMID 21107839
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1007/s00277-010-1121-z