Dendritic cell–activated CD44hiCD8+ T cells are defective in mediating acute graft-versus-host disease but retain graft-versus-leukemia activity

Y Zhang, G Joe, J Zhu, R Carroll, B Levine, E Hexner… - Blood, 2004 - ashpublications.org
Y Zhang, G Joe, J Zhu, R Carroll, B Levine, E Hexner, C June, SG Emerson
Blood, 2004ashpublications.org
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
CD44hiCD8+ effector/memory T cells were functionally defective in inducing GVHD,
whereas CD44loCD8+ naive phenotype T cells were extremely potent GVHD inducers …
Abstract
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 CD44hiCD8+ effector/memory T cells were functionally defective in inducing GVHD, whereas CD44loCD8+ naive phenotype T cells were extremely potent GVHD inducers. Depletion of CD44loCD8+ T cells from host DC-stimulated T cells before transplantation prevented GVHD without impairing their antitumor activity in vivo. Compared with CD44loCD8+ T cells, CD44hiCD8+ 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.
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