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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

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Title: 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
Authors: Asanuma, Shinsuke Browse this author
Tanaka, Junji Browse this author →KAKEN DB
Sugita, Junichi Browse this author
Kosugi, Mizuha Browse this author
Shiratori, Souichi Browse this author
Wakasa, Kentarou Browse this author
Shono, Yusuke Browse this author
Shigematsu, Akio Browse this author
Kondo, Takeshi Browse this author →KAKEN DB
Kobayashi, Takahiko Browse this author →KAKEN DB
Asaka, Masahiro Browse this author →KAKEN DB
Imamura, Masahiro Browse this author →KAKEN DB
Keywords: Regulatory T cells
Cord blood
Issue Date: Jun-2011
Publisher: Springer Berlin / Heidelberg
Journal Title: Annals of Hematology
Volume: 90
Issue: 6
Start Page: 617
End Page: 624
Publisher DOI: 10.1007/s00277-010-1121-z
PMID: 21107839
Abstract: 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.
Rights: The original publication is available at
Type: article (author version)
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 田中 淳司

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