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Donor-specific CD8+ Foxp3+ T cells protect skin allografts and facilitate induction of conventional CD4+ Foxp3+ regulatory T cells.

Publication ,  Journal Article
Lerret, NM; Houlihan, JL; Kheradmand, T; Pothoven, KL; Zhang, ZJ; Luo, X
Published in: Am J Transplant
September 2012

CD4(+) regulatory T cells play a critical role in tolerance induction in transplantation. CD8(+) suppressor T cells have also been shown to control alloimmune responses in preclinical and clinical models. However, the exact nature of the CD8(+) suppressor T cells, their induction and mechanism of function in allogeneic transplantation remain elusive. In this study, we show that functionally suppressive, alloantigen-specific CD8(+) Foxp3(+) T cells can be induced and significantly expanded by stimulating naïve CD8(+) T cells with donor dendritic cells in the presence of IL-2, TGF-β1 and retinoic acid. These CD8(+) Foxp3(+) T cells express enhanced levels of CTLA-4, CCR4 and CD103, inhibit the up-regulation of costimulatory molecules on dendritic cells, and suppress CD4 and CD8 T cell proliferation and cytokine production in a donor-specific and contact-dependent manner. Importantly, upon adoptive transfer, the induced CD8(+) Foxp3(+) T cells protect full MHC-mismatched skin allografts. In vivo, the CD8(+) Foxp3(+) T cells preferentially traffic to the graft draining lymph node where they induce conventional CD4(+) Foxp3(+) T cells and concurrently suppress effector T cell expansion. We conclude that donor-specific CD8(+) Foxp3(+) suppressor T cells can be induced and exploited as an effective form of cell therapy for graft protection in transplantation.

Duke Scholars

Published In

Am J Transplant

DOI

EISSN

1600-6143

Publication Date

September 2012

Volume

12

Issue

9

Start / End Page

2335 / 2347

Location

United States

Related Subject Headings

  • Tissue Donors
  • Surgery
  • Skin Transplantation
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Forkhead Transcription Factors
  • Cell Differentiation
  • CD8-Positive T-Lymphocytes
  • CD4-Positive T-Lymphocytes
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lerret, N. M., Houlihan, J. L., Kheradmand, T., Pothoven, K. L., Zhang, Z. J., & Luo, X. (2012). Donor-specific CD8+ Foxp3+ T cells protect skin allografts and facilitate induction of conventional CD4+ Foxp3+ regulatory T cells. Am J Transplant, 12(9), 2335–2347. https://doi.org/10.1111/j.1600-6143.2012.04120.x
Lerret, N. M., J. L. Houlihan, T. Kheradmand, K. L. Pothoven, Z. J. Zhang, and X. Luo. “Donor-specific CD8+ Foxp3+ T cells protect skin allografts and facilitate induction of conventional CD4+ Foxp3+ regulatory T cells.Am J Transplant 12, no. 9 (September 2012): 2335–47. https://doi.org/10.1111/j.1600-6143.2012.04120.x.
Lerret NM, Houlihan JL, Kheradmand T, Pothoven KL, Zhang ZJ, Luo X. Donor-specific CD8+ Foxp3+ T cells protect skin allografts and facilitate induction of conventional CD4+ Foxp3+ regulatory T cells. Am J Transplant. 2012 Sep;12(9):2335–47.
Lerret, N. M., et al. “Donor-specific CD8+ Foxp3+ T cells protect skin allografts and facilitate induction of conventional CD4+ Foxp3+ regulatory T cells.Am J Transplant, vol. 12, no. 9, Sept. 2012, pp. 2335–47. Pubmed, doi:10.1111/j.1600-6143.2012.04120.x.
Lerret NM, Houlihan JL, Kheradmand T, Pothoven KL, Zhang ZJ, Luo X. Donor-specific CD8+ Foxp3+ T cells protect skin allografts and facilitate induction of conventional CD4+ Foxp3+ regulatory T cells. Am J Transplant. 2012 Sep;12(9):2335–2347.
Journal cover image

Published In

Am J Transplant

DOI

EISSN

1600-6143

Publication Date

September 2012

Volume

12

Issue

9

Start / End Page

2335 / 2347

Location

United States

Related Subject Headings

  • Tissue Donors
  • Surgery
  • Skin Transplantation
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Forkhead Transcription Factors
  • Cell Differentiation
  • CD8-Positive T-Lymphocytes
  • CD4-Positive T-Lymphocytes