Recipient-type specific CD4+CD25+ regulatory T cells favor immune reconstitution and control graft-versus-host disease while maintaining graft-versus-leukemia

J Clin Invest. 2003 Dec;112(11):1688-96. doi: 10.1172/JCI17702.


CD4+CD25+ regulatory T cells (Treg's) play a pivotal role in preventing organ-specific autoimmune diseases and in inducing tolerance to allogeneic organ transplants. We and others recently demonstrated that high numbers of Treg's can also modulate graft-versus-host disease (GVHD) if administered in conjunction with allogeneic hematopoietic stem cell transplantation in mice. In a clinical setting, it would be impossible to obtain enough freshly purified Treg's from a single donor to have a therapeutic effect. Thus, we performed regulatory T cell expansion ex vivo by stimulation with allogeneic APCs, which has the additional effect of producing alloantigen-specific regulatory T cells. Here we show that regulatory T cells specific for recipient-type alloantigens control GVHD while favoring immune reconstitution. Irrelevant regulatory T cells only mediate a partial protection from GVHD. Preferential survival of specific regulatory T cells, but not of irrelevant regulatory T cells, was observed in grafted animals. Additionally, the use of specific regulatory T cells was compatible with some form of graft-versus-tumor activity. These data suggest that recipient-type specific Treg's could be preferentially used in the control of GVHD in future clinical trials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Transplantation
  • CD4 Antigens / analysis*
  • Female
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / pathology
  • Graft vs Host Disease / prevention & control*
  • Graft vs Leukemia Effect / immunology*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred Strains
  • Receptors, Interleukin-2 / analysis*
  • T-Lymphocyte Subsets / immunology*
  • Transplantation, Homologous


  • CD4 Antigens
  • Receptors, Interleukin-2