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GVHD‐Associated Enteropathy and Endotoxemia in F 1 ‐Hybrid Recipients of NK1.1‐Depleted Grafts
Author(s) -
Ellison C. A.,
Amadeo R. J. J.,
Gartner J. G.
Publication year - 2001
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.2001.00963.x
Subject(s) - enteropathy , lipopolysaccharide , immunology , tumor necrosis factor alpha , immune system , medicine , ileum , in vitro , biology , disease , biochemistry
Our previous work using a C57BL/6→(C57BL/6 × DBA/2)F 1 ‐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)‐γ production and lipopolysaccharide (LPS)‐induced tumour necrosis factor (TNF)‐α 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 × DBA/2)F 1 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.