The oral histopathological and immunological characteristics of a xenogeneic mouse chronic graft-versus-host disease model.

Abstract

Oral lesions are important clinical manifestations of chronic graft-verse-host disease (cGVHD). However, the oral characteristics of cGVHD mouse model are not yet clear. This study aims to demonstrate oral histopathological and immunological characteristics of a xenogeneic cGVHD mouse model. 2.5×106 , 5.0×106 , 7.5×106 , and 10.0×106 human peripheral blood mononuclear cells (hPBMCs) were intravenously transplanted into NCG mice to induce cGVHD. After transplantation, clinical observations were recorded. Tissue samples from salivary glands and oral mucosa were stained with H&E, Masson Trichrome, and immunofluorescence, and the histopathology of oral tissues was scored according to our modified criteria. NCG mice showed signs of cGVHD onset after transplantation. The oral histopathological lesion incidences in each group were 37.50%, 50.00%, 62.50%, and 75.00%, respectively. Oral histopathological lesion incidence and histopathological scores were positively correlated with the amount of infused hPBMCs. Epithelial atrophy, epithelial cells vacuolar degeneration, and basal cells liquefaction denaturation were observed in oral mucosa, and acinar destruction and collagen deposition were observed in the salivary glands. Human CD45+ , CD4+ , CD8+ , IL-17+ , and FoxP3+ cells infiltrated into oral tissues. In the 5.0×106 hPBMCs group, oral histopathological changes mainly began between days 30 and 45 post-transplantation, and became more severe after day 45. The oral histopathological scores also gradually increased. Inflammation in oral mucosa epithelium and salivary glands, and CD4+ and CD8+ T cells dominating infiltration are the main oral features in the xenogeneic cGVHD mouse model. The severity of oral histopathological lesions shows a dose and time correlation. These may be helpful to oral cGVHD research.