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

Masako Murai, Hiroyuki Yoneyama, Taichi Ezaki, Makoto Suematsu, Yuya Terashima, Akihisa Harada, Hiromasa Hamada, Hitoshi Asakura, Hiromichi Ishikawa, Kouji Matsushima

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213 Citations (Scopus)

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 FI 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 α4β7-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.

Original languageEnglish
Pages (from-to)154-160
Number of pages7
JournalNature Immunology
Volume4
Issue number2
DOIs
Publication statusPublished - 2003 Feb 1

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ASJC Scopus subject areas

  • Immunology

Cite this

Murai, M., Yoneyama, H., Ezaki, T., Suematsu, M., Terashima, Y., Harada, A., Hamada, H., Asakura, H., Ishikawa, H., & Matsushima, K. (2003). Peyer's patch is the essential site in initiating murine acute and lethal graft-versus-host reaction. Nature Immunology, 4(2), 154-160. https://doi.org/10.1038/ni879