Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1990 Feb;79(2):279–284. doi: 10.1111/j.1365-2249.1990.tb05191.x

Experimental studies of immunologically mediated enteropathy. V. Destructive enteropathy during an acute graft-versus-host reaction in adult BDF1 mice.

A M Mowat 1, M V Felstein 1
PMCID: PMC1534741  PMID: 2138068

Abstract

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.

Full text

PDF
279

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Borland A., Mowat A. M., Parrott D. M. Augmentation of intestinal and peripheral natural killer cell activity during the graft-versus-host reaction in mice. Transplantation. 1983 Nov;36(5):513–519. doi: 10.1097/00007890-198311000-00009. [DOI] [PubMed] [Google Scholar]
  2. Felstein M. V., Mowat A. M. Experimental studies of immunologically mediated enteropathy: IV. Correlation between immune effector mechanisms and type of enteropathy during a GvHR in neonatal mice of different ages. Clin Exp Immunol. 1988 Apr;72(1):108–112. [PMC free article] [PubMed] [Google Scholar]
  3. Ferguson A., MacDonald T. T. Effects of local delayed hypersensitivity on the small intestine. Ciba Found Symp. 1977 Apr 26;(46):305–327. doi: 10.1002/9780470720288.ch15. [DOI] [PubMed] [Google Scholar]
  4. Guy-Grand D., Vassalli P. Gut injury in mouse graft-versus-host reaction. Study of its occurrence and mechanisms. J Clin Invest. 1986 May;77(5):1584–1595. doi: 10.1172/JCI112474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Kubota E., Ishikawa H., Saito K. Modulation of F1 cytotoxic potentials by GvHR. Host- and donor-derived cytotoxic lymphocytes arise in the unirradiated F1 host spleens under the condition of GvHR-associated immunosuppression. J Immunol. 1983 Sep;131(3):1142–1148. [PubMed] [Google Scholar]
  6. MacDonald T. T., Ferguson A. Hypersensitivity reactions in the small intestine. III. The effects of allograft rejection and of graft-versus-host disease on epithelial cell kinetics. Cell Tissue Kinet. 1977 Jul;10(4):301–312. [PubMed] [Google Scholar]
  7. Mowat A. M., Borland A., Parrott D. M. Hypersensitivity reactions in the small intestine. VII. Induction of the intestinal phase of murine graft-versus-host-reaction by Lyt 2- T cells activated by I-A alloantigens. Transplantation. 1986 Feb;41(2):192–198. [PubMed] [Google Scholar]
  8. Mowat A. M., Felstein M. V., Baca M. E. Experimental studies of immunologically mediated enteropathy. III. Severe and progressive enteropathy during a graft-versus-host reaction in athymic mice. Immunology. 1987 Jun;61(2):185–188. [PMC free article] [PubMed] [Google Scholar]
  9. Mowat A. M., Felstein M. V., Borland A., Parrott D. M. Experimental studies of immunologically mediated enteropathy. Development of cell mediated immunity and intestinal pathology during a graft-versus-host reaction in irradiated mice. Gut. 1988 Jul;29(7):949–956. doi: 10.1136/gut.29.7.949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Mowat A. M., Ferguson A. Hypersensitivity reactions in the small intestine. 6. Pathogenesis of the graft-versus-host reaction in the small intestinal mucosa of the mouse. Transplantation. 1981 Sep;32(3):238–243. doi: 10.1097/00007890-198109000-00011. [DOI] [PubMed] [Google Scholar]
  11. Mowat A. M., Ferguson A. Intraepithelial lymphocyte count and crypt hyperplasia measure the mucosal component of the graft-versus-host reaction in mouse small intestine. Gastroenterology. 1982 Aug;83(2):417–423. [PubMed] [Google Scholar]
  12. Pals S. T., Radaszkiewicz T., Gleichmann E. Allosuppressor- and allohelper-T cells in acute and chronic graft-vs-host disease. IV. Activation of donor allosuppressor cells is confined to acute GVHD. J Immunol. 1984 Apr;132(4):1669–1678. [PubMed] [Google Scholar]
  13. Roder J. C., Karre K., Kiessling R. Natural killer cells. Prog Allergy. 1981;28:66–159. [PubMed] [Google Scholar]
  14. Rolink A. G., Radaszkiewicz T., Pals S. T., van der Meer W. G., Gleichmann E. Allosuppressor and allohelper T cells in acute and chronic graft-vs-host disease. I. Alloreactive suppressor cells rather than killer T cells appear to be the decisive effector cells in lethal graft-vs.-host disease. J Exp Med. 1982 May 1;155(5):1501–1522. doi: 10.1084/jem.155.5.1501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. SIMONSEN M. Graft versus host reactions. Their natural history, and applicability as tools of research. Prog Allergy. 1962;6:349–467. [PubMed] [Google Scholar]
  16. Van Elven E. H., Rolink A. G., Veen F. V., Gleichmann E. Capacity of genetically different T lymphocytes to induce lethal graft-versus-host disease correlates with their capacity to generate suppression but not with their capacity to generate anti-F1 killer cells. A non-H-2 locus determines the inability to induce lethal graft-versus-host disease. J Exp Med. 1981 Jun 1;153(6):1474–1488. doi: 10.1084/jem.153.6.1474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Via C. S., Sharrow S. O., Shearer G. M. Role of cytotoxic T lymphocytes in the prevention of lupus-like disease occurring in a murine model of graft-vs-host disease. J Immunol. 1987 Sep 15;139(6):1840–1849. [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES