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

Blood. 2009 May 28;113(22):5644-9. doi: 10.1182/blood-2008-12-191833. Epub 2009 Mar 31.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animal Experimentation
  • Animals
  • Antigen-Presenting Cells / immunology*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Bone Marrow Transplantation / immunology*
  • CD11 Antigens / genetics
  • Dendritic Cells / immunology*
  • Dendritic Cells / physiology
  • Female
  • Isoantigens / immunology*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic

Substances

  • CD11 Antigens
  • Isoantigens