SEARCH:   Advanced

Blood, 15 November 2006, Vol. 108, No. 10, pp. 3611-3619. Prepublished online as a Blood First Edition Paper on August 3, 2006; DOI 10.1182/blood-2006-04-017467. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-04-017467v1 108/10/3611    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 Xu, H. Articles by Ildstad, S. T. Search for Related Content PubMed PubMed Citation Articles by Xu, H. Articles by Ildstad, S. T. Related Collections Immunobiology Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Humoral immunity is the dominant barrier for allogeneic bone marrow engraftment in sensitized recipients Hong Xu, Paula M. Chilton, Michael K. Tanner, Yiming Huang, Carrie L. Schanie, Mariano Dy-Liacco, Jun Yan, and Suzanne T. Ildstad From the Institute for Cellular Therapeutics and the James Graham Brown Cancer Center, University of Louisville, Louisville, KY. We evaluated the relative contribution of the humoral and cellular arms of the immune response to bone marrow cells transplanted into sensitized recipients. We report here for the first time that humoral immunity contributes predominantly to allosensitization. Although the major role for nonmyeloablative conditioning is to control alloreactive host T cells in nonsensitized recipients, strikingly, none of the strategies directed primarily at T-cell alloreactivity enhanced engraftment in sensitized mice. In evaluating the mechanism behind this barrier, we found that humoral immunity plays a critical role in the rejection of allogeneic marrow in sensitized recipients. Adoptive transfer of as little as 25 µL serum from sensitized mice abrogated engraftment in secondary naive recipients. With the use of µMT mice as recipients, we found that T-cell-mediated immunity plays a secondary but still significant role in allorejection. Targeting of T cells in sensitized B-cell-deficient µMT mice enhanced alloengraftment. Moreover, both T- and B-cell tolerance were achieved in sensitized recipients when allochimerism was established, as evidenced by the acceptance of second donor skin grafts and loss of circulating donor-specific Abs. These findings have important implications for the management of sensitized transplant recipients and for xenotransplantation in which B-cell reactivity is a predominant barrier. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. H. Horne, J. M. Zimmerer, M. G. Fisher, K. E. Lunsford, G. Nadasdy, T. Nadasdy, N. van Rooijen, and G. L. Bumgardner Critical Role of Effector Macrophages in Mediating CD4-Dependent Alloimmune Injury of Transplanted Liver Parenchymal Cells J. Immunol., July 15, 2008; 181(2): 1224 - 1231. [Abstract] [Full Text] [PDF] H. Xu, J. Yan, Y. Huang, P. M. Chilton, C. Ding, C. L. Schanie, L. Wang, and S. T. Ildstad Costimulatory blockade of CD154-CD40 in combination with T-cell lymphodepletion results in prevention of allogeneic sensitization Blood, March 15, 2008; 111(6): 3266 - 3275. [Abstract] [Full Text] [PDF] D. H. Fowler B-ware of allosensitized graft rejection Blood, February 1, 2007; 109(3): 851 - 852. [Full Text] [PDF]

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020