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Blood, 30 April 2009, Vol. 113, No. 18, pp. 4458-4467. Prepublished online as a Blood First Edition Paper on February 12, 2009; DOI 10.1182/blood-2008-06-165506. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-06-165506v1 113/18/4458    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Pillai, A. B. Articles by Strober, S. Search for Related Content PubMed PubMed Citation Articles by Pillai, A. B. Articles by Strober, S. Related Collections Immunobiology Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Host natural killer T cells induce an interleukin-4–dependent expansion of donor CD4+CD25+Foxp3+ T regulatory cells that protects against graft-versus-host disease Asha B. Pillai1,2, Tracy I. George3, Suparna Dutt1, and Samuel Strober1 1 Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, CA; 2 Division of Bone Marrow Transplantation and Cellular Therapy, Department of Oncology, St Jude Children's Research Hospital, Memphis, TN; and 3 Department of Pathology, Stanford University School of Medicine, CA Although CD4+CD25+ T cells (T regulatory cells [Tregs]) and natural killer T cells (NKT cells) each protect against graft-versus-host disease (GVHD), interactions between these 2 regulatory cell populations after allogeneic bone marrow transplantation (BMT) have not been studied. We show that host NKT cells can induce an in vivo expansion of donor Tregs that prevents lethal GVHD in mice after conditioning with fractionated lymphoid irradiation (TLI) and anti–T-cell antibodies, a regimen that models human GVHD-protective nonmyeloablative protocols using TLI and antithymocyte globulin (ATG), followed by allogeneic hematopoietic cell transplantation (HCT). GVHD protection was lost in NKT-cell–deficient J18–/– hosts and interleukin-4 (IL-4)–/– hosts, or when the donor transplant was Treg depleted. Add-back of donor Tregs or wild-type host NKT cells restored GVHD protection. Donor Treg proliferation was lost in IL-4–/– hosts or when IL-4–/– mice were used as the source of NKT cells for adoptive transfer, indicating that host NKT cell augmentation of donor Treg proliferation after TLI/antithymocyte serum is IL-4 dependent. Our results demonstrate that host NKT cells and donor Tregs can act synergistically after BMT, and provide a mechanism by which strategies designed to preserve host regulatory cells can augment in vivo donor Treg expansion to regulate GVHD after allogeneic HCT. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. E. Kohrt, B. B. Turnbull, K. Heydari, J. A. Shizuru, G. G. Laport, D. B. Miklos, L. J. Johnston, S. Arai, W.-K. Weng, R. T. Hoppe, et al. TLI and ATG conditioning with low risk of graft-versus-host disease retains antitumor reactions after allogeneic hematopoietic cell transplantation from related and unrelated donors Blood, July 30, 2009; 114(5): 1099 - 1109. [Abstract] [Full Text] [PDF]

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