Peyer's patch is the essential site in initiating murine acute and lethal graft-versus-host reaction.
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.
Murai
Masako
M
Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Japan.
Yoneyama
Hiroyuki
H
Ezaki
Taichi
T
Suematsu
Makoto
M
Terashima
Yuya
Y
Harada
Akihisa
A
Hamada
Hiromasa
H
Asakura
Hitoshi
H
Ishikawa
Hiromichi
H
Matsushima
Kouji
K
D000208:Acute Disease; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015815:Cell Adhesion Molecules; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control; D006087:Graft vs Host Reaction; D007136:Immunoglobulins; D016898:Interferon-alpha / Q000037:antagonists & inhibitors; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D018448:Models, Immunological; D009088:Mucoproteins / Q000037:antagonists & inhibitors; D010581:Peyer's Patches / Q000276:immunology*; D019713:Receptors, CCR5 / Q000172:deficiency / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D016898:Interferon-alpha; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D019713:Receptors, CCR5