Apoptosis of keratinocytes is associated with infiltration of CD8+ lymphocytes and accumulation of Ki67 antigen

In 18 allogeneic blood/marrow transplanted (BMT) cases, skin biopsies were taken for acute GVHD diagnosis. In 14 cases clinical and histopathology data were consistent with acute GVHD with toxic lesions in four cases, All skin biopsies were stained for the presence of apoptotic cells (TUNEL technique). Nine patients' skin biopsies were positive for this stain. Apoptotic cells were seen in epidermal cells of the epidermis and in hair follicles, The presence of apoptotic cells was associated with (1) advanced stage (greater than or equal to II grade) acute GVHD (P = 0.015) and (2) heavy mononuclear cell infiltration (P = 0.015), predominantly of CD8(+) cells (P = 0.025), Ki67 immunoreactivity of epidermal cells was different in the epidermis having and lacking apoptotic cells. Ki67 MoAb staining of epidermal cells revealed that nuclei were enlarged and stained stronger in biopsies with than biopsies without apoptotic cells (P = 0.008), Cyclin A positive cells were in a high proportion and cdc2-positive cells in a low proportion in patients' biopsies with acute GVHD and toxic lesions. In addition cyclin A accumulation was seen in keratinocytes in GVHD biopsies. Therefore, mitosis of skin cells is impaired, likely due to the genotoxic effect of conditioning, which renders the cells susceptible to acute GVHD-associated apoptotic damage.