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

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193 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)7393-7398
Number of pages6
JournalJournal of Immunology
Volume172
Issue number12
DOIs
Publication statusPublished - Jun 15 2004
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Duffner, U. A., Maeda, Y., Cooke, K. R., Reddy, P., Ordemann, R., Liu, C., Ferrara, J. L. M., & Teshima, T. (2004). Host dendritic cells alone are sufficient to initiate acute graft-versus-host disease. Journal of Immunology, 172(12), 7393-7398. https://doi.org/10.4049/jimmunol.172.12.7393