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...

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Bibliographic Details
Published in:Blood 2009-05, Vol.113 (22), p.5644-5649
Main Authors: Markey, Kate A., Banovic, Tatjana, Kuns, Rachel D., Olver, Stuart D., Don, Alistair L.J., Raffelt, Neil C., Wilson, Yana A., Raggatt, Liza J., Pettit, Allison R., Bromberg, Jonathan S., Hill, Geoffrey R., MacDonald, Kelli P.A.
Format: Article
Language:English
Subjects:
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Animal Experimentation
Animals
Antigen-Presenting Cells - immunology
B-Lymphocytes - immunology
B-Lymphocytes - pathology
Biological and medical sciences
Bone Marrow Transplantation - immunology
Bone marrow, stem cells transplantation. Graft versus host reaction
CD11 Antigens - genetics
Dendritic Cells - immunology
Dendritic Cells - physiology
Female
Hematologic and hematopoietic diseases
Isoantigens - immunology
Lymphocyte Activation
Medical sciences
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic
Transfusions. Complications. Transfusion reactions. Cell and gene therapy
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Summary: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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2008-12-191833