Submitted December 1, 2008
Accepted March 22, 2009
Conventional dendritic cells are the critical donor APC presenting alloantigen after experimental BMT
Kate A Markey, Tatjana Banovic, Rachel D Kuns, Stuart D Olver, Alistair LJ Don, Neil C Raffelt, Yana A Wilson, Liza J Raggatt, Allison R Pettit, Jonathan S Bromberg, Geoffrey R Hill, and Kelli PA MacDonald*
The Queensland Institute of Medical Research, Bone Marrow Transplantation Laboratory, Brisbane, QLD, Australia
The University of Queensland, Centre for Clinical Research, Brisbane, QLD, Australia
Mount Sinai School of Medicine, New York, NY, United States
* Corresponding author; email: kelli.macdonald{at}qimr.edu.au.
We have quantified the relative contribution of donor APC populations to alloantigen presentation after BMT by using transgenic T cells that can respond to host-derived alloantigen presented within donor MHC. We also utilized additional transgenic/knockout donor mice and/or monoclonal antibodies that allowed conditional depletion of conventional DC (cDC), plasmacytoid DC (pDC), macrophages or B cells. Using these systems we demonstrate that donor cDC are the critical population presenting alloantigen after BMT while pDC 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.
