Conventional dendritic cells are the critical donor APC presenting alloantigen after experimental bone marrow transplantation.
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.
Markey
Kate A
KA
Bone Marrow Transplantation Laboratory, Queensland Institute of Medical Research, Brisbane, Australia.
Banovic
Tatjana
T
Kuns
Rachel D
RD
Olver
Stuart D
SD
Don
Alistair L J
AL
Raffelt
Neil C
NC
Wilson
Yana A
YA
Raggatt
Liza J
LJ
Pettit
Allison R
AR
Bromberg
Jonathan S
JS
Hill
Geoffrey R
GR
MacDonald
Kelli P A
KP