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

T Teshima, R Ordemann, P Reddy, S Gagin, C Liu… - Nature medicine, 2002 - nature.com
T Teshima, R Ordemann, P Reddy, S Gagin, C Liu, KR Cooke, JLM Ferrara
Nature medicine, 2002nature.com
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 …
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.
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