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 Blood, 28 May 2009, Vol. 113, No. 22, pp. 5644-5649.
Prepublished online as a Blood First Edition Paper on March 31, 2009; DOI 10.1182/blood-2008-12-191833.

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TRANSPLANTATION

Conventional dendritic cells are the critical donor APC presenting alloantigen after experimental bone marrow transplantation

Kate A. Markey1,2, Tatjana Banovic1, Rachel D. Kuns1, Stuart D. Olver1, Alistair L. J. Don1, Neil C. Raffelt1, Yana A. Wilson1, Liza J. Raggatt3, Allison R. Pettit3, Jonathan S. Bromberg4, Geoffrey R. Hill1, and Kelli P. A. MacDonald1

1 Bone Marrow Transplantation Laboratory, Queensland Institute of Medical Research, Brisbane, Australia; 2 University of Queensland School of Medicine, Brisbane, Australia; 3 Centre for Clinical Research, University of Queensland, Brisbane, Australia; and 4 Mount Sinai School of Medicine, New York, NY

We have quantified the relative contribution of donor antigen-presenting cell populations to alloantigen presentation after bone marrow transplantation (BMT) by using transgenic T cells that can respond to host-derived alloantigen presented within the donor major histocompatibility complex. We also used additional transgenic/knockout donor mice and/or monoclonal antibodies that allowed conditional depletion of conventional dendritic cells (cDCs), plasmacytoid DC (pDCs), macrophages, or B cells. Using these systems, we demonstrate that donor cDCs are the critical population presenting alloantigen after BMT, whereas pDCs and macrophages do not make a significant contribution in isolation. In addition, alloantigen presentation was significantly enhanced in the absence of donor B cells, confirming a regulatory role for these cells early after transplantation. These data have major implications for the design of therapeutic strategies post-BMT, and suggest that cDC depletion and the promotion of B-cell reconstitution may be beneficial tools for the control of alloreactivity.


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