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Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2002-03-0872. This Article Full Text (PDF) All Versions of this Article: 2002-03-0872v1 100/9/3400    most recent Alert me when this article is cited Alert me if a correction is posted 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 Taylor, P. A Articles by Blazar, B. R Search for Related Content PubMed PubMed Citation Articles by Taylor, P. A Articles by Blazar, B. R Social Bookmarking                   What's this? Submitted March 19, 2002 Accepted May 19, 2002 The Combined Effects of Calcineurin Inhibitors or Sirolimus with Anti-CD40L mAb on Alloengraftment under Nonmyeloablative Conditions Patricia A Taylor, Christopher J Lees, Jessica M Wilson, Michael J Ehrhardt, Matthew T Campbell, Randolph J Noelle, and Bruce R Blazar* Division of Bone Marrow Transplantation, University of Minnesota Cancer Center and Department of Pediatrics, Minneapolis, MN, USA Department of Microbiology, Dartmouth Medical College, Hanover, NH, USA * Corresponding author; email: blaza001{at}tc.umn.edu. The immunosuppressive drugs Cyclosporine A (CsA), tacrolimus or sirolimus were analyzed as single agents and in combination with anti-CD40L mAb for their effects on alloengraftment in mice conditioned with minimal total body irradiation (TBI). Whereas anti-CD40L mAb facilitated chimerism, neither sirolimus nor CsA resulted in significant alloengraftment. However, sirolimus was synergistic with anti-CD40L mAb for inducing donor chimerism. Contrary to expectations, CsA, a TCR signaling inhibitor, did not abrogate anti-CD40L mAb-facilitated engraftment but rather increased engraftment in anti-CD40L mAb-treated mice. Although tacrolimus alone or with anti-CD40L mAb resulted in similar levels of donor chimerism, donor T cell reconstitution was very low in tacrolimus-treated mice. At 1 week after transplantation, CsA decreased thymic numbers more profoundly than sirolimus or tacrolimus in anti-CD40L mAb-treated recipients. In contrast, only sirolimus resulted in a decrease in host splenic T cell numbers in anti-CD40L mAb-treated recipients. Importantly, sirolimus and anti-CD40L mAb induced profound donor tolerance with 100% acceptance of donor skin grafts placed early after bone marrow transplantation (BMT). In contrast, anti-CD40L mAb alone or in combination with CsA resulted in 12% donor skin graft acceptance early (1 month) and 60% later (3 months) after BMT. These data have clinical relevance and indicate that immunosuppressive pharmacological agents enhance anti-CD40L mAb-facilitated alloengraftment and tolerance induction under nonmyeloablative conditioning. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Xu, Y. Huang, P. M. Chilton, L.-R. Hussain, M. K. Tanner, J. Yan, and S. T. Ildstad Strategic Nonmyeloablative Conditioning: CD154:CD40 Costimulatory Blockade at Primary Bone Marrow Transplantation Promotes Engraftment for Secondary Bone Marrow Transplantation after Engraftment Failure J. Immunol., November 1, 2008; 181(9): 6616 - 6624. [Abstract] [Full Text] [PDF] D. C. Gondek, V. DeVries, E. C. Nowak, L.-F. Lu, K. A. Bennett, Z. A. Scott, and R. J. 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