Transfer of regulatory T cells generated ex vivo modifies graft rejection through induction of tolerogenic CD4+CD25+ cells in the recipient

Song Guo Zheng, Lingzhong Meng, Ju Hua Wang, Meguru Watanabe, Mark L. Barr, Donald V. Cramer, J. Dixon Gray, David A. Horwitz

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Certain CD4+CD25+ T cells can induce and maintain T-cell non-responsiveness to donor alloantigens and have therapeutic potential in solid organ transplantation. Peripheral CD4+CD25- cells alloactivated with IL-2 and transforming growth factor β (TGF-β) ex vivo express the transcription factor FoxP3, and become potent antigen-specific CD4+CD25- suppressor cells. Here we report that the transfer of TGF-β-induced regulatory CD4+ and CD8+ T cells (Tregs) co-incident with transplantation of a histoincompatible heart resulted in extended allograft survival. To account for this result, we injected non-transplanted mice with a single dose of CD4+ and CD8+ Tregs and transferred donor cells every 2 weeks to mimic the continuous stimulation of a transplant. We observed increased splenic CD4+CD25+ cells that were of recipient origin. These cells rendered the animals non-responsive to donor alloantigens by an antigen-specific and cytokine-dependent mechanism of action. Both the increased number of CD4+CD25+ cells and their tolerogenic effect were dependent on continued donor antigen boosting. Thus, Tregs generated ex vivo can act like a vaccine that generates host suppressor cells with the potential to protect MHC-mismatched organ grafts from rejection.

Original languageEnglish (US)
Pages (from-to)279-289
Number of pages11
JournalInternational Immunology
Volume18
Issue number2
DOIs
StatePublished - Feb 1 2006

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Graft Rejection
Regulatory T-Lymphocytes
Isoantigens
T-Lymphocytes
Transplants
Antigens
CD4 Antigens
Transforming Growth Factors
Organ Transplantation
Interleukin-2
Allografts
Transcription Factors
Vaccines
Transplantation
Cytokines

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Zheng, Song Guo ; Meng, Lingzhong ; Wang, Ju Hua ; Watanabe, Meguru ; Barr, Mark L. ; Cramer, Donald V. ; Gray, J. Dixon ; Horwitz, David A. / Transfer of regulatory T cells generated ex vivo modifies graft rejection through induction of tolerogenic CD4+CD25+ cells in the recipient. In: International Immunology. 2006 ; Vol. 18, No. 2. pp. 279-289.
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Transfer of regulatory T cells generated ex vivo modifies graft rejection through induction of tolerogenic CD4+CD25+ cells in the recipient. / Zheng, Song Guo; Meng, Lingzhong; Wang, Ju Hua; Watanabe, Meguru; Barr, Mark L.; Cramer, Donald V.; Gray, J. Dixon; Horwitz, David A.

In: International Immunology, Vol. 18, No. 2, 01.02.2006, p. 279-289.

Research output: Contribution to journalArticle

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