@article {1051061,
	title = {Programmed death ligand-1 expression on donor T cells drives graft-versus-host disease lethality},
	journal = {J Clin Invest},
	volume = {126},
	number = {7},
	year = {2016},
	month = {2016 Jul 01},
	pages = {2642-60},
	abstract = {Programmed death ligand-1 (PD-L1) interaction with PD-1 induces T cell exhaustion and is a therapeutic target to enhance immune responses against cancer and chronic infections. In murine bone marrow transplant models, PD-L1 expression on host target tissues reduces the incidence of graft-versus-host disease (GVHD). PD-L1 is also expressed on T cells; however, it is unclear whether PD-L1 on this population influences immune function. Here, we examined the effects of PD-L1 modulation of T cell function in GVHD. In patients with severe GVHD, PD-L1 expression was increased on donor T cells. Compared with mice that received WT T cells, GVHD was reduced in animals that received T cells from Pdl1-/- donors. PD-L1-deficient T cells had reduced expression of gut homing receptors, diminished production of inflammatory cytokines, and enhanced rates of apoptosis. Moreover, multiple bioenergetic pathways, including aerobic glycolysis, oxidative phosphorylation, and fatty acid metabolism, were also reduced in T cells lacking PD-L1. Finally, the reduction of acute GVHD lethality in mice that received Pdl1-/- donor cells did not affect graft-versus-leukemia responses. These data demonstrate that PD-L1 selectively enhances T cell-mediated immune responses, suggesting a context-dependent function of the PD-1/PD-L1 axis, and suggest selective inhibition of PD-L1 on donor T cells as a potential strategy to prevent or ameliorate GVHD.},
	issn = {1558-8238},
	doi = {10.1172/JCI85796},
	author = {Saha, Asim and O{\textquoteright}Connor, Roddy S and Thangavelu, Govindarajan and Lovitch, Scott B and Dandamudi, Durga Bhavani and Wilson, Caleph B and Vincent, Benjamin G and Tkachev, Victor and Pawlicki, Jan M and Furlan, Scott N and Kean, Leslie S and Aoyama, Kazutoshi and Taylor, Patricia A and Panoskaltsis-Mortari, Angela and Foncea, Rocio and Ranganathan, Parvathi and Devine, Steven M and Burrill, Joel S and Guo, Lili and Sacristan, Catarina and Snyder, Nathaniel W and Blair, Ian A and Milone, Michael C and Dustin, Michael L and Riley, James L and Bernlohr, David A and Murphy, William J and Fife, Brian T and Munn, David H and Miller, Jeffrey S and Serody, Jonathan S and Freeman, Gordon J and Sharpe, Arlene H and Turka, Laurence A and Blazar, Bruce R}
}
