Host dendritic cells alone are sufficient to initiate acute graft-versus-host disease

Ulrich A. Duffner, Yoshinobu Maeda, Kenneth R. Cooke, Pavan Reddy, Rainer Ordemann, Chen Liu, James L.M. Ferrara, Takanori Teshima


207 被引用数 (Scopus)


Alloantigen expression on host APCs is essential to initiate graft-vs-host disease (GVHD); however, critical APC subset remains to be elucidated. We compared the ability of dendritic cells (DCs) and B cells to initiate acute GVHD by an add-back study of MHC class II-expressing APCs (II+/+) into MHC class II-defficient (II-/-) mice that were resistant to CD4-dependent GVHD. Injection of host-derived, but not donor-derived, II +/+ DCs or host-derived II+/+ B cells, was sufficient to break GVHD resistance of II-/- mice and induced lethal acute GVHD. By contrast, host-derived II+/+ B cells, both naive and LPS stimulated, failed to induce activation or tolerance of donor CD4+ T cells. Similarly, in a model of CD8-dependent GVHD across MHC class I mismatch injection of allogeneic DCs, but not B cells, induced robust proliferation of donor CD8+ T cells and broke GVHD resistance of chimeric recipients in which APCs were syngeneic to donors. These results demonstrate that host-derived DCs are critical in priming donor CD4+ and CD8 + T cells to cause GVHD, and selective targeting of host DCs may be a promising strategy to prevent GVHD.

ジャーナルJournal of Immunology
出版ステータスPublished - 6月 15 2004

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学


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