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


Journal Article

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 beta (TGF-beta) ex vivo express the transcription factor FoxP3, and become potent antigen-specific CD4+CD25- suppressor cells. Here we report that the transfer of TGF-beta-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.

Full Text

Cited Authors

  • Zheng, SG; Meng, L; Wang, JH; Watanabe, M; Barr, ML; Cramer, DV; Gray, JD; Horwitz, DA

Published Date

  • February 2006

Published In

Volume / Issue

  • 18 / 2

Start / End Page

  • 279 - 289

PubMed ID

  • 16415106

Pubmed Central ID

  • 16415106

International Standard Serial Number (ISSN)

  • 0953-8178

Digital Object Identifier (DOI)

  • 10.1093/intimm/dxh368


  • eng

Conference Location

  • England