TY - JOUR
T1 - Novel regulatory therapies for prevention of Graft-versus-host disease
AU - Leventhal, Joseph
AU - Huang, Yiming
AU - Xu, Hong
AU - Goode, Idona
AU - Ildstad, Suzanne T.
N1 - Funding Information:
The authors thank Dr. Haval Shirwan for a review of the manuscript and helpful comments; Dr. Yujie Wen for extensive reference research; and Carolyn DeLautre for manuscript preparation. This work was supported in part by the following grants: NIH R01 DK069766 and NIH 5RO1 HL063442. This publication was also made possible by Award No.W81XWH-07-1-0185 and W81XWH-09-2-0124 from the U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick, MD,21702-5014 (Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the Office of Army Research); and the Commonwealth of Kentucky Research Challenge Trust Fund.
PY - 2012/5/15
Y1 - 2012/5/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84861526563&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84861526563&partnerID=8YFLogxK
U2 - 10.1186/1741-7015-10-48
DO - 10.1186/1741-7015-10-48
M3 - Review article
C2 - 22587383
AN - SCOPUS:84861526563
SN - 1741-7015
VL - 10
JO - BMC Medicine
JF - BMC Medicine
M1 - 48
ER -