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  • Title: Acute graft-versus-host disease does not require alloantigen expression on host epithelium.
    Author: Teshima T, Ordemann R, Reddy P, Gagin S, Liu C, Cooke KR, Ferrara JL.
    Journal: Nat Med; 2002 Jun; 8(6):575-81. PubMed ID: 12042807.
    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-alpha 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.
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