Involvement of OX40-OX40L interactions in the intestinal manifestations of the murine acute graft-versus-host disease

Gastroenterology. 1998 Nov;115(5):1205-15. doi: 10.1016/s0016-5085(98)70092-7.


Background & aims: The intestinal histology of murine semiallogeneic graft-versus-host (GVH) disease is characterized by lymphocytic infiltrates, crypt hyperplasia, and villous atrophy. Mechanisms of T cell-mediated changes of the mucosal architecture were investigated.

Methods: The rate of cellular apoptosis and proliferation, changes in the composition of extracellular matrix (ECM), and the role of OX40-OX40L interactions in the pathogenesis of villous atrophy and crypt hyperplasia were examined.

Results: The rate of apoptosis and the number of proliferating cells were significantly increased in GVH animals compared with control animals. In addition, expression of tenascin, an ECM component, was down-regulated in GVH animals. Inhibition of OX40-OX40L interactions in GVH animals by administration of an OX40-Ig fusion protein completely prevented the development of crypt hyperplasia and villous atrophy in GVH animals. Tenascin expression was up-regulated in OX40-Ig-treated mice compared with GVH animals, suggesting an important function of this ECM component in mucosal repair.

Conclusions: The OX40-OX40L interaction is crucial in the pathogenesis of GVH, a T cell-mediated intestinal disease. The data suggest that the ECM component tenascin is probably relevant for the regeneration and maintenance of intestinal tissue architecture.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Apoptosis / physiology
  • Cell Division / physiology
  • Epithelial Cells / physiology
  • Extracellular Matrix Proteins / metabolism
  • Graft vs Host Disease / pathology
  • Graft vs Host Disease / physiopathology*
  • Immunoglobulins / physiology
  • Intestine, Small / pathology
  • Intestines / pathology
  • Intestines / physiopathology*
  • Jejunum / pathology
  • Jejunum / physiopathology
  • Kinetics
  • Membrane Glycoproteins*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • OX40 Ligand
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor / physiology
  • Regeneration / physiology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / physiology
  • Tumor Necrosis Factors


  • Extracellular Matrix Proteins
  • Immunoglobulins
  • Membrane Glycoproteins
  • OX40 Ligand
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor
  • Tnfrsf4 protein, mouse
  • Tnfsf4 protein, mouse
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Tumor Necrosis Factors