Recipient-type specific CD4+CD25+ regulatory T cells favor immune reconstitution and control graft-versus-host disease while maintaining graft-versus-leukemia
versus-host disease (GVHD) (2).To date, an immunosuppressive regimen based on cyclosporin A associated with methotrexate and/or corticosteroids administered in the months following HSCT is the most efficient preventive treatment but remains only partially effective (3).Procedures in which T cells are depleted from the transplant can prevent GVHD but have also revealed the important role that donor T cells play in the prevention of graft rejection (4), in lowering risks of infection, and in the graft-versus-leukemia (GVL) and/or the graft-versus-tumor (GVT) effects (5).Thus, administering donor allogeneic T cells without causing GVHD remains the key challenge of allogeneic HSCT.Recently, a particular subpopulation of CD4 + T cells, which constitutively expresses the IL-2 receptor chain (CD25) and which constitutes 5%-10% of the whole CD4 + T cell pool in mice and humans, has been identified for its crucial role in the control of autoimmune processes (6, 7).In different models in which mice were rendered deficient for this CD4 + CD25 + regulatory T cell (Treg) population, multiple T cell-mediated, organ-specific autoimmune diseases were observed (refs.6, 8-10, and for review see refs.11-13).One particularly important property of these Treg's is their capacity to mediate in vitro suppression of conventional CD4 + or CD8 + T cells (14-16).This property of the so-called Treg's was demonstrated in mice and humans.Recent reports have shown that Treg's play a major role in tolerance induction to allogeneic transplants (17-20).We and others have also demonstrated that