The murine forestomach: a sensitive site for graft-versus-host disease.

The minor histoincompatible mouse radiation chimera provides a useful model of graft-versus-host disease (GVHD) paralleling conditions in human marrow transplant recipients. While studying the B10.D2/BALB/c model, we noted that a graft-versus-host reaction of particular severity develops in the forestomach near the squamocolumnar junction. Comparison of the dyskeratotic index of this epithelium with that of the skin of the same animal revealed the forestomach to be a more sensitive site for detection of GVHD. In normal mice, both basal forestomach squamous epithelium and cells in the lamina propria expressed class II antigens. During the course of GVHD, class II antigen expression was elevated in the squamous epithelium of the forestomach, the columnar epithelium associated with the stomach, and cells within the associated lamina propria. The demonstration here that the squamocolumnar junction (considered to be a stem cell region for the maintenance of adjacent forestomach squamous epithelium) appears to be a particularly sensitive target tissue in GVHD and earlier identification of other epithelial target tissues of GVHD (hair follicles and rete ridges of epidermis, bile ductules of liver, and crypt cells of the gut) collectively support the hypothesis that GVHD tends to target sites of epithelial proliferation overlying epithelial stem cells.