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

A Trenado, F Charlotte, S Fisson… - The Journal of …, 2003 - Am Soc Clin Investig
A Trenado, F Charlotte, S Fisson, M Yagello, D Klatzmann, BL Salomon, JL Cohen
The Journal of clinical investigation, 2003Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation