Acute graft-versus-host disease does not require alloantigen expression on host epithelium

Takanori Teshima, Rainer Ordemann, Pavan Reddy, Svetlana Gagin, Chen Liu, Kenneth R. Cooke, James L.M. Ferrara

Research output: Contribution to journalArticle

Abstract

Alloantigen expression on host antigen-presenting cells (APCs) is essential to initiate graft-versus-host disease (GvHD); therefore, alloantigen expression on host target epithelium is also thought to be essential for tissue damage. We tested this hypothesis in mouse models of GvHD using bone-marrow chimeras in which either major histocompatibility complex class I or class II alloantigen was expressed only on APCs. We found that acute GvHD does not require alloantigen expression on host target epithelium and that neutralization of tumor necrosis factor-α and interleukin-1 prevents acute GvHD. These results pertain particularly to CD4-mediated GvHD but also apply, at least in part, to CD8-mediated GvHD. These results challenge current paradigms about the antigen specificity of GvHD effector mechanisms and confirm the central roles of both host APCs and inflammatory cytokines in acute GvHD.

Original languageEnglish (US)
Pages (from-to)575-581
Number of pages7
JournalNature medicine
Volume8
Issue number6
DOIs
StatePublished - Jun 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Teshima, T., Ordemann, R., Reddy, P., Gagin, S., Liu, C., Cooke, K. R., & Ferrara, J. L. M. (2002). Acute graft-versus-host disease does not require alloantigen expression on host epithelium. Nature medicine, 8(6), 575-581. https://doi.org/10.1038/nm0602-575