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

Author:

Markey Kate A.12,Banovic Tatjana1,Kuns Rachel D.1,Olver Stuart D.1,Don Alistair L. J.1,Raffelt Neil C.1,Wilson Yana A.1,Raggatt Liza J.3,Pettit Allison R.3,Bromberg Jonathan S.4,Hill Geoffrey R.1,MacDonald Kelli P. A.1

Affiliation:

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

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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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