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

Nat Immunol. 2003 Feb;4(2):154-60. doi: 10.1038/ni879. Epub 2003 Jan 13.

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 alpha(4)beta(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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Adhesion Molecules*
  • Disease Models, Animal
  • Graft vs Host Disease / etiology*
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / prevention & control
  • Graft vs Host Reaction*
  • Immunoglobulins
  • Interferon-alpha / antagonists & inhibitors
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Knockout
  • Models, Immunological
  • Mucoproteins / antagonists & inhibitors
  • Peyer's Patches / immunology*
  • Receptors, CCR5 / deficiency
  • Receptors, CCR5 / genetics
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Cell Adhesion Molecules
  • Immunoglobulins
  • Interferon-alpha
  • Madcam1 protein, mouse
  • Mucoproteins
  • Receptors, CCR5