2024-03-29T00:47:25Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/493342022-11-17T02:08:08Zhdl_2115_20040hdl_2115_121Expansion of CD4+CD25+ regulatory T cells from cord blood CD4+ cells using the common γ-chain cytokines (IL-2 and IL-15) and rapamycinAsanuma, ShinsukeTanaka, JunjiSugita, JunichiKosugi, MizuhaShiratori, SouichiWakasa, KentarouShono, YusukeShigematsu, AkioKondo, TakeshiKobayashi, TakahikoAsaka, MasahiroImamura, MasahiroRegulatory T cellsIL-2IL-15RapamycinCord blood491Rapamycin 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.Springer Berlin / HeidelbergJournal Articleapplication/pdfhttp://hdl.handle.net/2115/49334https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/49334/1/AoH90-6_617-624.pdf0939-5555Annals of Hematology9066176242011-06enginfo:pmid/21107839info:doi/10.1007/s00277-010-1121-zThe original publication is available at www.springerlink.comauthor