Nature Immunology
4, 154 - 160 (2003)
Published online: 13 January 2003; | doi:10.1038/ni879
There is a Corrigendum (May 2003) associated with this Article.
Peyer's patch is the essential site in initiating murine acute and lethal graft-versus-host reactionMasako Murai1, 2, Hiroyuki Yoneyama1, 2, Taichi Ezaki3, Makoto Suematsu4, Yuya Terashima1, Akihisa Harada1, Hiromasa Hamada5, Hitoshi Asakura2, Hiromichi Ishikawa5
& Kouji Matsushima11
Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan. 2
Department of Internal Medicine, Niigata University School of Medicine, Niigata-shi, Niigata 951-8122, Japan. 3
Department of Anatomy & Developmental Biology, School of Medicine, Tokyo Women's Medical University, Shinjyuku-ku, Tokyo 162-8666, Japan. 4
Department of Biochemistry, School of Medicine, Keio University, Shinjyuku-ku, Tokyo 160-8582, Japan. 5
Department of Microbiology, School of Medicine, Keio University, Shinjyuku-ku, Tokyo 160-8582, Japan.
Correspondence should be addressed to Kouji Matsushima koujim@m.u-tokyo.ac.jpAcute 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  4 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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R on the lamina propria stromal cells of the gut is required for IgA production
