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Blood, 15 March 2008, Vol. 111, No. 6, pp. 3266-3275. Prepublished online as a Blood First Edition Paper on September 7, 2007; DOI 10.1182/blood-2006-10-053801. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-10-053801v1 111/6/3266    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 Google Scholar Articles by Xu, H. Articles by Ildstad, S. T. PubMed PubMed Citation Articles by Xu, H. Articles by Ildstad, S. T. Related Collections Transplantation Signal Transduction Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Costimulatory blockade of CD154-CD40 in combination with T-cell lymphodepletion results in prevention of allogeneic sensitization Hong Xu1, Jun Yan2, Yiming Huang1, Paula M. Chilton1, Chuanlin Ding2, Carrie L. Schanie1, Li Wang2, and Suzanne T. Ildstad1 1 Institute for Cellular Therapeutics, University of Louisville, Louisville, KY; 2 James Graham Brown Cancer Center, University of Louisville, Louisville, KY Sensitization is a critical unresolved challenge in transplantation. We show for the first time that blockade of CD154 alone or combined with T-cell depletion prevents sensitization. Allogeneic skin grafts were rejected by recipients treated with anti-β T-cell receptor (TCR), anti-CD154, anti-OX40L, or anti–inducible costimulatory pathway (ICOS) mAb alone with a kinetic similar to untreated recipients. However, the production of anti–donor MHC antibody was prevented in mice treated with anti-CD154 mAb only, suggesting a specific role for the CD154-CD40 pathway in B-cell activation. The impairment of T cell–dependent B-cell responses by blocking CD154 occurs through inhibiting activation of T and B cells and secretion of IFN- and IL-10. Combined treatment with both anti-CD154 and anti–β TCR abrogated antidonor antibody production and resulted in prolonged skin graft survival, suggesting the induction of both T- and B-cell tolerance with prevention of allogeneic sensitization. In addition, we show that the tolerance induced by combined treatment was nondeletional. Moreover, these sensitization-preventive strategies promote bone marrow engraftment in recipients previously exposed to donor alloantigen. These findings may be clinically relevant to prevent allosensitization with minimal toxicity and point to humoral immunity as playing a dominant role in alloreactivity in sensitized recipients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Xu, J. Yan, and S. T. Ildstad Xenotransplantation: a step closer to reality? Blood, December 1, 2007; 110(12): 3815 - 3815. [Full Text] [PDF]

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