The role of cell-mediated cytotoxicity in acute GVHD after MHC-matched allogeneic bone marrow transplantation in mice.
The role of cell-mediated cytotoxicity in the complex pathophysiology of graft-versus-host disease (GVHD) has remained poorly defined for several decades. We transplanted T cells from Fas-ligand (FasL)-defective and perforin-deficient mutant donor mice into lethally irradiated MHC-matched allogeneic recipient mice to characterize the role of cell-mediated cytotoxicity in GVHD. Although recipients of allogeneic FasL-defective donor T cells underwent severe GVHD-associated cachexia, they exhibited only minimal signs of hepatic and cutaneous GVHD pathology. Recipients of perforin-deficient allogeneic donor T cells developed signs of acute GVHD, but the time of onset was significantly delayed. These findings demonstrate that Fas-mediated anti-recipient cytotoxicity may be critical for the development of hepatic and cutaneous GVHD, but is not required for GVHD-associated cachexia. In addition, perforin-mediated anti-recipient cytotoxicity appears to play an important role in the kinetics of GVHD pathophysiology, but is not required for GVHD-associated tissue damage.
Baker
M B
MB
Department of Microbiology and Immunology, University of Miami School of Medicine, Florida 33101, USA.
Altman
N H
NH
Podack
E R
ER
Levy
R B
RB
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D006086:Graft vs Host Disease / Q000276:immunology*; D006650:Histocompatibility Testing; D016130:Immunophenotyping; D017710:Lymphocyte Transfusion; D008285:Major Histocompatibility Complex; D008562:Membrane Glycoproteins / Q000172:deficiency; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012867:Skin / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014184:Transplantation, Homologous; D019014:fas Receptor / Q000276:immunology*
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D019014:fas Receptor; D054353:Perforin