APOPTOSIS IS THE PREDOMINANT FORM OF EPITHELIAL TARGET-CELL INJURY INACUTE EXPERIMENTAL GRAFT-VERSUS-HOST DISEASE

Cutaneous and mucosal epithelial cells are primary targets of injury i n acute graft-vessus-host disease (GVHD), the principal complication o f allogeneic bone marrow transplantation. Recent experimental data in skin suggest that early lesions may precede morphologic evidence of di rect infiltration by effector cells, The purpose of this study was to further elucidate the mechanism and kinetics of epithelial injury in a cute GVHD produced in mouse strains (B10.BR/CBA) receiving bone marrow transplants across minor histocompatibility loci. Skin and tongue muc osa of hosts receiving CD8 T-cell-enriched, whole T-cell-enriched, or T-cell-depleted bone marrow transplants were sequentially harvested an d studied histologically and by the terminal uridine deoxynucleotidyl transferase end ligation technique to detect apoptotic cells. Apoptosi s involving putative stem cells is the predominant form of cellular in jury in acute experimental GVHD. Although apoptosis correlated with th e onset of lymphocyte infiltration relatively late in CD8-mediated dis ease, apoptosis was bimodal in whole T-cell-mediated disease, with an early peak that preceded histologic evidence of lymphocyte infiltratio n. These findings establish a central role for apoptosis in epithelial cell injury in acute GVHD and indicate that T-cell composition of the donor marrow inoculum may influence the pattern and kinetics of epith elial damage.