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

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  • A Corrigendum to this article was published on 01 May 2003

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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Acknowledgements

We thank J.J. Oppenheim, K. Matsuno, S. Ishikawa, M. Haino and C. Vestergaard for helpful discussions and S. Fujita for assistance in animal surgery. This work was supported by Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists (M.M.), by Grant-in-Aid for Creative Scientific Research, the Japan Society for the Promotion of Science (13GS0015) and Special Coordination Fund for Promoting Science and Technology, Ministry of Education, Culture, Sport, Science and Technology (H.I.) and by a grant from Solution Oriented Research for Science and Technology (SORST), Japan Science and Technology Corporation (K.M.).

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The authors declare no competing financial interests.

Correspondence to Kouji Matsushima.

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Figure 1: Early and prominent infiltration of donor CD8+ T cells into SED regions of host PPs.
Figure 2: Characterization of donor CD8+ T cells that infiltrate into SED regions of host PPs.
Figure 3: Production of CCR5−/− mice and analysis of CCR5−/− lymphocytes.
Figure 4: CCR5–CCL5 and α4β7–MAdCAM-1 interactions are implicated in the induction of a-GVHR.
Figure 5: Flow cytometric and immunohistochemical analyses of lymphocytes that reside in BDF1 mice with and without PPs.
Figure 6: Induction of acute and lethal GVHR is abolished in hosts that lack PPs.