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