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Blood, 15 March 2005, Vol. 105, No. 6, pp. 2577-2584. Prepublished online as a Blood First Edition Paper on October 21, 2004; DOI 10.1182/blood-2004-04-1340. This Article Full Text (PDF) All Versions of this Article: 2004-04-1340v1 105/6/2577    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 Ildstad, S. T Articles by Ray, M. B Search for Related Content PubMed PubMed Citation Articles by Ildstad, S. T Articles by Ray, M. B Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 8, 2004 Accepted September 22, 2004 Preconditioning of NOD mice with anti-CD8 mAb and co-stimulatory blockade enhances chimerism and tolerance and prevents diabetes while depletion of -TCR+ and CD4+ cells negates the effect Suzanne T Ildstad*, Paula M Chilton, Hong Xu, Michele A Domenick, and Mukunda B Ray Institute for Cellular Therapeutics, University of Louisville, Louisville, KY, USA Attending Surgeon, Kent General Hospital, Dover, DE, USA Department of Pathology, University of Louisville, Louisville, KY, USA * Corresponding author; email: stilds01{at}louisville.edu. Bone marrow transplantation blocks diabetes pathogenesis and reverses autoimmunity in NOD mice. However, there is a greater barrier to engraftment in the context of autoimmunity. In the present studies, we characterized which recipient cells influence engraftment in prediabetic NOD mice, with the goal to replace myelotoxic conditioning with antigen-specific deletion of reactive host cells. Preconditioning of NOD mice with anti-CD8 and anti-CD154 monoclonal antibodies (mAb) synergistically enhanced engraftment and significantly reduced the minimum TBI dose for engraftment. Strikingly, preconditioning with anti-CD4 mAb significantly impaired engraftment, negating the beneficial effect of anti-CD8, and resulted in a requirement for more TBI-based conditioning compared to controls conditioned with TBI alone. Similarly, more TBI was required when anti-TCR mAb was administered as preconditioning. The addition of anti-CD152 to CD154 preconditioning abrogated the engraftment-enhancing effect of anti-CD154. Taken together, these data indicate a role for CD4+ regulatory T cells in vivo which require signaling via CD152 in the induction of chimerism and tolerance in NOD recipients. Notably, disease-prevention and reversal of autoimmunity was absolutely correlated with the establishment of chimerism. These studies have important implications for the design of novel clinical approaches to treat type 1 diabetes. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. V. Serreze, M. A. Osborne, Y.-G. Chen, H. D. Chapman, T. Pearson, M. A. Brehm, and D. L. Greiner Partial versus Full Allogeneic Hemopoietic Chimerization Is a Preferential Means to Inhibit Type 1 Diabetes as the Latter Induces Generalized Immunosuppression J. Immunol., November 15, 2006; 177(10): 6675 - 6684. [Abstract] [Full Text] [PDF]

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