Peyer's patch is the essential site in initiating murine acute and lethal graft-versus-host reaction
2003; Nature Portfolio; Volume: 4; Issue: 2 Linguagem: Inglês
10.1038/ni879
ISSN1529-2916
AutoresMasako Murai, Hiroyuki Yoneyama, Taichi Ezaki, Makoto Suematsu, Yuya Terashima, Akihisa Harada, Hiromasa Hamada, Hitoshi Asakura, Hiromichi Ishikawa, Kouji Matsushima,
Tópico(s)T-cell and B-cell Immunology
ResumoAcute 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 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.
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