Tags

Type your tag names separated by a space and hit enter

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.
Ann Hematol. 2011 Jun; 90(6):617-24.AH

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 interleukin (IL)-15 or IL-2 with transforming growth factor (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 forkhead box P3 (FoxP3) mRNA at a level about 100-fold higher and could suppress allogeneic mixed lymphocyte culture (MLC) 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 phosphoinositide 3-kinase regulator phosphatase and tensin homolog deleted on chromosome 10 (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.

Authors+Show Affiliations

Department of Hematology and Oncology, Hokkaido University Graduate School of Medicine, N15 W7, Kita-Ku, Sapporo, 060-8638, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Evaluation Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21107839

Citation

Asanuma, Shinsuke, et al. "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." Annals of Hematology, vol. 90, no. 6, 2011, pp. 617-24.
Asanuma S, Tanaka J, Sugita J, et al. 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. Ann Hematol. 2011;90(6):617-24.
Asanuma, S., Tanaka, J., Sugita, J., Kosugi, M., Shiratori, S., Wakasa, K., Shono, Y., Shigematsu, A., Kondo, T., Kobayashi, T., Asaka, M., & Imamura, M. (2011). 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. Annals of Hematology, 90(6), 617-24. https://doi.org/10.1007/s00277-010-1121-z
Asanuma S, et al. 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. Ann Hematol. 2011;90(6):617-24. PubMed PMID: 21107839.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Asanuma,Shinsuke, AU - Tanaka,Junji, AU - Sugita,Junichi, AU - Kosugi,Mizuha, AU - Shiratori,Souichi, AU - Wakasa,Kentarou, AU - Shono,Yusuke, AU - Shigematsu,Akio, AU - Kondo,Takeshi, AU - Kobayashi,Takahiko, AU - Asaka,Masahiro, AU - Imamura,Masahiro, Y1 - 2010/11/24/ PY - 2010/09/15/received PY - 2010/11/11/accepted PY - 2010/11/26/entrez PY - 2010/11/26/pubmed PY - 2011/7/2/medline SP - 617 EP - 24 JF - Annals of hematology JO - Ann. Hematol. VL - 90 IS - 6 N2 - 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 interleukin (IL)-15 or IL-2 with transforming growth factor (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 forkhead box P3 (FoxP3) mRNA at a level about 100-fold higher and could suppress allogeneic mixed lymphocyte culture (MLC) 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 phosphoinositide 3-kinase regulator phosphatase and tensin homolog deleted on chromosome 10 (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. SN - 1432-0584 UR - https://www.unboundmedicine.com/medline/citation/21107839/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_ L2 - https://dx.doi.org/10.1007/s00277-010-1121-z DB - PRIME DP - Unbound Medicine ER -