GVHD-associated enteropathy and endotoxemia in F1-hybrid recipients of NK1.1-depleted grafts.
Our previous work using a C57BL/6-->(C57BL/6 x DBA/2)F1-hybrid model of acute GVHD showed that mortality can be completely prevented if grafts are depleted of NK1.1+ cells in vitro. To achieve this protection, it was necessary to inject the donors with polyinosinic:polycytidylic acid 18 h before the graft was harvested. In another study, we showed that interferon (IFN)-gamma production and lipopolysaccharide (LPS)-induced tumour necrosis factor (TNF)-alpha release are markedly reduced in these recipients, suggesting that this treatment abrogates the Th1-mediated immune response that underlies the development of this disease. However, because it has also been hypothesized that cytotoxic NK1.1+ cells mediate injury to tissues targeted by the GVH reaction, we wished to determine whether NK1.1 depletion of the graft would also prevent the development of GVHD-associated enteropathy and endotoxemia. We therefore induced GVH reactions in (C57BL/6 x DBA/2)F1 hybrids using either untreated grafts from unstimulated C57BL/6 donors, or NK1.1-depleted grafts from poly I:C-stimulated donors. We identified intestinal lesions morphologically in sections of ileum collected from each group of recipients but not in control mice. We also compared endotoxin levels in the sera. Our results indicate that GVHD-associated enteropathy occurs in both groups of recipients, and that the levels of LPS in the sera do not differ significantly.
Ellison
C A
CA
Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada.
Amadeo
R J
RJ
Gartner
J G
JG
D000818:Animals; D000941:Antigens / Q000276:immunology*; D000950:Antigens, Ly; D000954:Antigens, Surface; D017690:Cell Transplantation; D003602:Cytotoxicity, Immunologic; D019446:Endotoxemia / Q000097:blood / Q000276:immunology*; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D007082:Ileum / Q000276:immunology / Q000473:pathology*; D007413:Intestinal Mucosa / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D008070:Lipopolysaccharides / Q000097:blood; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins / Q000276:immunology*; D014407:Tumor Cells, Cultured; D015431:Weight Loss
D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins