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

An Erratum to this article was published on 01 September 2002

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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Figure 1: MHC II−/− mice are resistant to CD4-mediated GvHD.
Figure 2: Host APCs alone are sufficient to stimulate allogeneic CD4+ T cells.
Figure 3: CD4-mediated GvHD does not require MHC class II alloantigen expression on host epithelium.
Figure 4: Neutralization of inflammatory cytokines prevents CD4+ T cell-mediated GvHD.
Figure 5: CD8-mediated GvHD does not require MHC class I alloantigen expression on host epithelium.

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Acknowledgements

This work was supported by NIH grants CA39542 (to J.L.M.F.) and HL03565-05 (to K.C.).

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Correspondence to James L. M. Ferrara.

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Teshima, T., Ordemann, R., Reddy, P. et al. Acute graft-versus-host disease does not require alloantigen expression on host epithelium. Nat Med 8, 575–581 (2002). https://doi.org/10.1038/nm0602-575

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