Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021831 (enteropathy)
 4,403 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As a means of investigating further the pathogenesis of intestinal immunopathology, we have attempted to produce a destructive enteropathy by inducing an acute graft-versus-host reaction (GVHR) in mature, immunocompetent mice. Adult (C57b1/10 X DBA/2)F1 (BDF1) mice given C57B1/10(B10) spleen cells develop a severe GVHR which is associated with marked weight loss and high mortality. In the intestine an initial phase of enteropathy characterized by intense crypt hyperplasia is replaced by more severe intestinal damage which includes villus atrophy and loss of intra-epithelial lymphocytes. These pathological alterations are paralleled by the generation of anti-host cytotoxic T lymphocytes (CTL), marked immunosuppression and the loss of natural killer (NK) cells. In contrast to these findings, adult BDF1 mice given DBA/2 donor cells do not develop an acute systemic GVHR and have no CTL or intestinal pathology, despite prolonged splenomegaly and enhanced NK cell activity. Thus, destructive enteropathy can be induced during a GVHR in intact hosts and our results confirm that this enteropathy has a biphasic pattern, with villus atrophy representing the progression of initial crypt hyperplasia in severe forms of disease associated with weight loss and specific CTL.
 ...
PMID:Experimental studies of immunologically mediated enteropathy. V. Destructive enteropathy during an acute graft-versus-host reaction in adult BDF1 mice. 213 68

We have attempted to investigate the relative roles of specific cytotoxic T lymphocytes (CTL) and allospecific suppressor T cells (Ts) in the systemic and intestinal manifestations of acute graft-versus-host reaction (GvHR) in mice. Treatment of adult (C57B1/10 x DBA/2)F1 (BDF1) mice with the suppressor cell-specific toxin 2'-deoxyguanosine (dGuo) inhibited the weight loss and mortality which normally occur after induction of GvHR and C57Bl donor cells. dGuo also delayed the development of a destructive enteropathy as typified by jejunal villus atrophy. Paradoxically, dGuo completely prevented villus atrophy during an acute GvHR in neonatal (CBA x BALB/c)F1 hosts, despite having only a slight ability to inhibit the systemic disease. In both models, dGuo had no effect on the generation of splenomegaly or anti-host CTL, and dGuo-treated mice with GvHR actually had increased proliferative alterations in the intestine, as assessed by crypt hyperplasia. In parallel, dGuo prevented the loss of NK cells which normally occurs in acute GvHR. Thus dGuo inhibits many of the destructive features of systemic and intestinal GvHR without affecting the development of CTL. We conclude that a dGuo-sensitive mechanism causes the transition from a proliferative to a destructive GvHR.
 ...
PMID:Experimental studies of immunologically mediated enteropathy. VI. Inhibition of acute intestinal graft-versus-host reaction in mice by 2'-deoxyguanosine. 214 36

In a study designed to determine which T-cell subsets are involved in the development of murine graft-versus-host disease (GVHD), a prospective histologic analysis of gastrointestinal involvement was performed. In C57BL/6JXDBA/2F1 (B6D2F1) recipients of DBA/2 donor spleen and bone marrow cells, the colonic histologic findings were found to be similar in many respects to the histologic findings reported in human colonic GVHD and were much more severe and diffuse than were the abnormalities of the small intestine. Host irradiation before transplantation was found to play an additive or synergistic role in the development of GVHD. Furthermore the histologic features noted in DBA/2----B6D2F1 murine colonic GVHD suggest that bone marrow and spleen cell transplantation in this strain combination may be a useful model for studying the immunologic mechanisms involved in human inflammatory bowel disease. Thus severe colonic disease noted during the course of DBA/2----B6D2F1 murine GVHD was found to have significant histopathologic similarities to both human GVHD enteropathy and other inflammatory diseases of the human colon.
 ...
PMID:Histologic similarity of murine colonic graft-versus-host disease (GVHD) to human colonic GVHD and inflammatory bowel disease. 224 Jan 58

This study was performed to characterize the intestinal lesions in chronic graft-versus-host disease (GVHD) in mice and to determine a possible role of intestinal intraepithelial lymphocytes (ilEL) in the development of these lesions. Chronic GVHD was induced by transfer of DBA/2 lymphocytes into non-irradiated (C57BL/10 x DBA/2)F1 (BDF1) recipients. There was mild to moderate mucosal oedema with multifocal mixed inflammatory cell infiltrations in the small intestine. The caecum was more severely affected with severe oedema, progressive loss of crypts and severe distortion of the mucosal architecture. The total number of ilEL did not change during the development of chronic GVHD, but there were alterations in the composition of the ilEL population. An increase of CD3+, Thy-1+ cells was accompanied by an increase of TCR alpha beta + cells and a decrease of TCR gamma delta + cells. There was no evidence of infiltration of donor lymphocytes into the intestinal epithelium as determined by the H2K haplotype of the ilEL. These lesions differ from previously described models of chronic GVHD, induced by DBA/2 donor lymphocytes in BDF1 recipients. We suggest that the haemopoietic organs that are used as the source of donor lymphocytes determine the outcome of the GVHD. Modulation of the composition of the donor lymphocyte population may be useful in the establishment of relevant animal models of human enteropathy.
 ...
PMID:Effect of chronic graft-versus-host disease on the intestine in adult BDF1 mice. 839 10

We have previously reported that a nonapeptide thymic hormone, facteur thymique serique (FTS), is involved in the differentiation and activation of intestinal intraepithelial lymphocytes (i-IEL) in mice. In this study, we examined the effect of FTS treatment on enteropathy in a murine model for acute graft-vs.-host disease (GVHD) induced by injection of parental C57BL/6 splenocytes into unirradiated (C57BL/6 x DBA/2) F1 hybrids. FTS treatment significantly protected mice from developing acute GVHD as assessed by mortality rate, splenomegaly and enteropathy. The infiltration of donor-derived TCR alpha beta i-IEL bearing CD8 alpha beta was significantly inhibited in the small intestine of FTS-treated mice, and the frequencies of apoptosis of crypt cells in the intestinal mucosa were decreased in these mice during acute GVHD. These results suggest that FTS treatment contributes to protection against enteropathy of acute GVHD. Thus, FTS may provide a useful approach to control acute GVHD after blood transfusion or bone marrow transplantation.
 ...
PMID:A thymic hormone protects mice from enteropathy during acute graft-versus-host disease. 944 31

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.
 ...
PMID:GVHD-associated enteropathy and endotoxemia in F1-hybrid recipients of NK1.1-depleted grafts. 1155 4