Recipient-type specific CD4+CD25+ regulatory T cells favor immune reconstitution and control graft-versus-host disease while maintaining graft-versus-leukemia.
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.
Trenado
Aurélie
A
Biologie et Thérapeutique des Pathologies Immunitaires, Centre National de la Recherche Scientifique, Université Pierre et Marie Curie, Unité Mixte de Recherche 7087, Hôpital Pitié-Salpêtrière, 83 boulevard de l'Hôpital, F-75651 Paris Cedex 13, France.
Charlotte
Frédéric
F
Fisson
Sylvain
S
Yagello
Micael
M
Klatzmann
David
D
Salomon
Benoit L
BL
Cohen
José L
JL
D000818:Animals; D016026:Bone Marrow Transplantation; D015704:CD4 Antigens / Q000032:analysis*; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014184:Transplantation, Homologous
D015704:CD4 Antigens; D015375:Receptors, Interleukin-2