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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
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 | IL-2 | IL-15 | Rapamycin | 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 www.springerlink.com |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/49334 |
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)
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Submitter: 田中 淳司
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