Ex vivo selection of recipient-type alloantigen-specific CD4+CD25+ immunoregulatory T cells for the control of graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation

Allogeneic hematopoietic stem-cell transplantation (HSCT) is the treatment of choice for many malignant and nonmalignant hematologic disorders. Donor T cells present in the hematopoietic stem-cell transplant improve engraftment and immune reconstitution and contribute to the graft-versus-leukemia effect, but are also responsible for the life-threatening graft-versus-host disease (GVHD). CD4(+)CD25(+) immunoregulatory T cells, which play a pivotal role in preventing organ-specific diseases, can also modulate GVHD if administered in equal numbers of T cells at the time of grafting. In this article, the authors describe a procedure of ex vivo selection and expansion of regulatory T cells specific for recipient-type alloantigens. These expanded regulatory T cells controlled GVHD. Their therapeutic use in HSCT should allow specific suppression of the activation of donor alloreactive T cells involved in GVHD while preserving the beneficial effects of other T cells.