title: Novel regulatory therapies for prevention of Graft-versus-host disease.
abstract: Graft-versus-host disease is one of the major transplant-related complications in allogeneic hematopoietic stem cell transplantation. Continued efforts have been made to prevent the occurrence of severe graft-versus-host disease by eliminating or suppressing donor-derived effector T cells. Conventional immunosuppression does not adequately prevent graft-versus-host disease, especially in mismatched transplants. Unfortunately, elimination of donor-derived T cells impairs stem cell engraftment, and delays immunologic reconstitution, rendering the recipient susceptible to post-transplant infections and disease relapse, with potentially lethal consequences. In this review, we discuss the role of dynamic immune regulation in controlling graft-versus-host disease, and how cell-based therapies are being developed using regulatory T cells and other tolerogenic cells for the prevention and treatment of graft-versus-host disease. In addition, advances in the design of cytoreductive conditioning regimens to selectively target graft-versus-host disease-inducing donor-derived T cells that have improved the safety of allogeneic stem cell transplantation are reviewed. Finally, we discuss advances in our understanding of the tolerogenic facilitating cell population, a phenotypically and functionally distinct population of bone marrow-derived cells which promote hematopoietic stem cell engraftment while reducing the risk of graft-versus-host disease.
authors.affiliation: Institute for Cellular Therapeutics, University of Louisville, Louisville, KY, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Leventhal
authors.forename: Yiming
authors.initials: Y
authors.lastname: Huang
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.forename: Idona
authors.initials: I
authors.lastname: Goode
authors.forename: Suzanne T
authors.initials: ST
authors.lastname: Ildstad
mesh_terms: D006086:Graft vs Host Disease / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007167:Immunotherapy / Q000379:methods*; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous / Q000009:adverse effects*