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

M Murai, H Yoneyama, T Ezaki, M Suematsu… - Nature …, 2003 - nature.com
M Murai, H Yoneyama, T Ezaki, M Suematsu, Y Terashima, A Harada, H Hamada…
Nature immunology, 2003nature.com
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 …
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 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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