Irradiation of the skin and systemic graft-versus-host disease synergize to produce cutaneous lesions.

In this report, the relationship between irradiation and graft-versus-host disease (GVHD)-induced cutaneous injury was investigated. Unirradiated F1 hybrid mice were grafted with irradiated skin and then injected with parental strain lymphoid cells to induce GVHD. Although low grade dermal lymphoid infiltrates were observed in unirradiated skin grafts of some GVH-reactive mice, and irradiated grafts of normal animals showed occasional fibrosis, only the irradiated grafts of GVH-reactive mice developed lesions consisting of vacuolar degeneration of the epidermal-dermal junction and necrotic keratinocytes accompanied by pronounced epidermal infiltrates, characteristic of clinical cutaneous GVHD. The results suggest that cutaneous irradiation exerts a permissive effect on lesion formation in the skin of mice undergoing GVHD. Furthermore, systemic irradiation, known to exacerbate the severity of GVHD, is not required. Cutaneous lesions may be triggered by radiation injury of keratinocytes, up-regulation of adhesion molecules on irradiated endothelium, destruction of protective radiosensitive intraepithelial lymphocytes, and radiation-induced priming of intradermal macrophages.