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Nat Immunol. 2003 Feb;4(2):154-60. Epub 2003 Jan 13.

Peyer's patch is the essential site in initiating murine acute and lethal graft-versus-host reaction.

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1
Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Japan.

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  • Nat Immunol. 2003 May;4(5):497.

Abstract

Acute graft-versus-host disease (a-GVHD) is initiated primarily by immunologically competent cytotoxic T cells (CTLs) that express anti-host specificities. However, the host lymphoid compartment in which these precursor CTLs are initially stimulated remains unclear. Here we show that gut Peyer's patches (PPs) are required to activate anti-host CTL responses in a well characterized murine acute graft-versus-host reaction (a-GVHR) model, involving transfer of parent lymphocytes into F1 hybrid recipients. The a-GVHR was prevented when recruitment of donor T cells into PP was interrupted either by disrupting the gene encoding chemokine receptor CCR5 or by blocking integrin alpha(4)beta(7)-MAdCAM-1 (mucosal vascular addressin) interactions. Mice deficient for PPs failed to develop a-GVHD in two models of disease induction. Thus, blockade of CTL generation in PPs might offer new strategies for circumventing a-GVHD.

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PMID:
12524535
DOI:
10.1038/ni879
[Indexed for MEDLINE]
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