Dendritic cell-activated CD44hiCD8+ T cells are defective in mediating acute graft-versus-host disease but retain graft-versus-leukemia activity.
Graft versus host disease (GVHD) is triggered by host antigen-presenting cells (APCs) that activate donor T cells to proliferate and differentiate, but which APC-activated donor T-cell subsets mediate GVHD versus beneficial antitumor effects is not known. Using a CD8(+) T cell-dependent mouse model of human GVHD, we found that host dendritic cell (DC)-induced CD44(hi)CD8(+) effector/memory T cells were functionally defective in inducing GVHD, whereas CD44(lo)CD8(+) naive phenotype T cells were extremely potent GVHD inducers. Depletion of CD44(lo)CD8(+) T cells from host DC-stimulated T cells before transplantation prevented GVHD without impairing their antitumor activity in vivo. Compared with CD44(lo)CD8(+) T cells, CD44(hi)CD8(+) T cells expressed high levels of Fas and were efficiently deleted in vivo following transplantation. These results suggest that ex vivo allogeneic DC stimulation of donor CD8(+) T cells may be useful for the prevention of GVHD and for optimizing antitumor therapies in vivo.
Zhang
Yi
Y
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Joe
Gerard
G
Zhu
Jiang
J
Carroll
Richard
R
Levine
Bruce
B
Hexner
Elizabeth
E
June
Carl
C
Emerson
Stephen G
SG
D000208:Acute Disease; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000379:methods; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D020544:Graft vs Leukemia Effect / Q000276:immunology; D018960:Hyaluronan Receptors; D008212:Lymphocyte Depletion / Q000379:methods; D051379:Mice; D008815:Mice, Inbred Strains; D016176:T-Lymphocyte Subsets / Q000276:immunology; D019014:fas Receptor
D018960:Hyaluronan Receptors; D019014:fas Receptor