CD4(+)CD25(+) immunoregulatory T Cells: new therapeutics for graft-versus-host disease.
CD4(+)CD25(+) immunoregulatory T cells play a pivotal role in preventing organ-specific autoimmune diseases and in tolerance induction to allogeneic organ transplants. We investigated whether these cells could also control graft-versus-host disease (GVHD), the main complication after allogeneic hematopoietic stem cell transplantation (HSCT). Here, we show that the few CD4(+)CD25(+) T cells naturally present in the transplant regulate GVHD because their removal from the graft dramatically accelerates this disease. Furthermore, the addition of freshly isolated CD4(+)CD25(+) T cells at time of grafting significantly delays or even prevents GVHD. Ex vivo-expanded CD4(+)CD25(+) regulatory T cells obtained after stimulation by allogeneic recipient-type antigen-presenting cells can also modulate GVHD. Thus, CD4(+)CD25(+) regulatory T cells represent a new therapeutic tool for controlling GVHD in allogeneic HSCT. More generally, these results outline the tremendous potential of regulatory T cells as therapeutics.
Cohen
José L
JL
Laboratoire de Biologie et Thérapeutique des Pathologies Immunitaires, Centre National de la Recherche Scientifique UMR 7087, Hôpital Pitié-Salpêtrière, 756651 Paris, France.
Trenado
Aurélie
A
Vasey
Douglas
D
Klatzmann
David
D
Salomon
Benoît L
BL
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D015704:CD4 Antigens / Q000032:analysis*; D006086:Graft vs Host Disease / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation; 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