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Rapamycin-conditioned donor dendritic cells differentiate CD4CD25Foxp3 T cells in vitro with TGF-beta1 for islet transplantation.

Publication ,  Journal Article
Pothoven, KL; Kheradmand, T; Yang, Q; Houlihan, JL; Zhang, H; Degutes, M; Miller, SD; Luo, X
Published in: Am J Transplant
August 2010

Dendritic cells (DCs) conditioned with the mammalian target of rapamycin (mTOR) inhibitor rapamycin have been previously shown to expand naturally existing regulatory T cells (nTregs). This work addresses whether rapamycin-conditioned donor DCs could effectively induce CD4(+)CD25(+)Foxp3(+) Tregs (iTregs) in cell cultures with alloantigen specificities, and whether such in vitro-differentiated CD4(+)CD25(+)Foxp3(+) iTregs could effectively control acute rejection in allogeneic islet transplantation. We found that donor BALB/c bone marrow-derived DCs (BMDCs) pharmacologically modified by the mTOR inhibitor rapamycin had significantly enhanced ability to induce CD4(+)CD25(+)Foxp3(+) iTregs of recipient origin (C57BL/6 (B6)) in vitro under Treg driving conditions compared to unmodified BMDCs. These in vitro-induced CD4(+)CD25(+)Foxp3(+) iTregs exerted donor-specific suppression in vitro, and prolonged allogeneic islet graft survival in vivo in RAG(-/-) hosts upon coadoptive transfer with T-effector cells. The CD4(+)CD25(+)Foxp3(+) iTregs expanded and preferentially maintained Foxp3 expression in the graft draining lymph nodes. Finally, the CD4(+)CD25(+)Foxp3(+) iTregs were further able to induce endogenous naïve T cells to convert to CD4(+)CD25(+)Foxp3(+) T cells. We conclude that rapamycin-conditioned donor BMDCs can be exploited for efficient in vitro differentiation of donor antigen-specific CD4(+)CD25(+)Foxp3(+) iTregs. Such in vitro-generated donor-specific CD4(+)CD25(+)Foxp3(+) iTregs are able to effectively control allogeneic islet graft rejection.

Duke Scholars

Published In

Am J Transplant

DOI

EISSN

1600-6143

Publication Date

August 2010

Volume

10

Issue

8

Start / End Page

1774 / 1784

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta1
  • T-Lymphocytes, Regulatory
  • Surgery
  • Sirolimus
  • Mice, Inbred C57BL
  • Mice
  • Islets of Langerhans Transplantation
  • Interleukin-2 Receptor alpha Subunit
  • Graft Rejection
  • Forkhead Transcription Factors
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Pothoven, K. L., Kheradmand, T., Yang, Q., Houlihan, J. L., Zhang, H., Degutes, M., … Luo, X. (2010). Rapamycin-conditioned donor dendritic cells differentiate CD4CD25Foxp3 T cells in vitro with TGF-beta1 for islet transplantation. Am J Transplant, 10(8), 1774–1784. https://doi.org/10.1111/j.1600-6143.2010.03199.x
Pothoven, K. L., T. Kheradmand, Q. Yang, J. L. Houlihan, H. Zhang, M. Degutes, S. D. Miller, and X. Luo. “Rapamycin-conditioned donor dendritic cells differentiate CD4CD25Foxp3 T cells in vitro with TGF-beta1 for islet transplantation.Am J Transplant 10, no. 8 (August 2010): 1774–84. https://doi.org/10.1111/j.1600-6143.2010.03199.x.
Pothoven KL, Kheradmand T, Yang Q, Houlihan JL, Zhang H, Degutes M, et al. Rapamycin-conditioned donor dendritic cells differentiate CD4CD25Foxp3 T cells in vitro with TGF-beta1 for islet transplantation. Am J Transplant. 2010 Aug;10(8):1774–84.
Pothoven, K. L., et al. “Rapamycin-conditioned donor dendritic cells differentiate CD4CD25Foxp3 T cells in vitro with TGF-beta1 for islet transplantation.Am J Transplant, vol. 10, no. 8, Aug. 2010, pp. 1774–84. Pubmed, doi:10.1111/j.1600-6143.2010.03199.x.
Pothoven KL, Kheradmand T, Yang Q, Houlihan JL, Zhang H, Degutes M, Miller SD, Luo X. Rapamycin-conditioned donor dendritic cells differentiate CD4CD25Foxp3 T cells in vitro with TGF-beta1 for islet transplantation. Am J Transplant. 2010 Aug;10(8):1774–1784.
Journal cover image

Published In

Am J Transplant

DOI

EISSN

1600-6143

Publication Date

August 2010

Volume

10

Issue

8

Start / End Page

1774 / 1784

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta1
  • T-Lymphocytes, Regulatory
  • Surgery
  • Sirolimus
  • Mice, Inbred C57BL
  • Mice
  • Islets of Langerhans Transplantation
  • Interleukin-2 Receptor alpha Subunit
  • Graft Rejection
  • Forkhead Transcription Factors