Loss of Programmed Death Ligand-1 Expression on Donor T Cells Lessens Acute Graft-Versus-Host Disease Lethality

• Published in: Blood 2015-12, Vol.126 (23), p.147-147
• Main Authors: Saha, Asim, O'Connor, Roddy S., Thangavelu, Govindarajan, Lovitch, Scott B., Dandamudi, Durga Bhavani, Wilson, Caleph B., Vincent, Benjamin G., Aoyama, Kazutoshi, Taylor, Patricia A., Panoskaltsis-Mortari, Angela, Foncea, Rocio, Burrill, Joel S., Guo, Lili, Sacristan, Catarina, Furlan, Scott N., Snyder, Nathaniel W., Blair, Ian A., Milone, Michael C., Dustin, Michael L., Riley, James L., Bernlohr, David A., Turka, Laurence A., Murphy, William J., Fife, Brian T., Munn, David H., Miller, Jeffrey S., Serody, Jonathan S., Kean, Leslie, Freeman, Gordon J., Sharpe, Arlene H., Blazar, Bruce R.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V126.23.147.147

The PD-1/PD-L1 pathway plays an important role in regulation of alloimmune responses and in induction and maintenance of peripheral tolerance. Because GVHD is driven by donor T cells and PD-L1 expression can be markedly elevated on T cells during activation, we investigated the functional significance of PD-L1 expressed by donor T cells in regulating murine models of acute GVHD. PD-L1 expression was up-regulated on donor CD4 and CD8 T cells during GVHD. We considered the possibility that PD-L1 expression on activated donor T cells might inhibit GVHD by down regulating donor anti-host T cell responses, consistent with PD-L1 co-inhibitory activity when expressed on host parenchymal cells during GVHD. Surprisingly, T cell mediated GVHD lethality was markedly reduced in recipients of PD-L1-/- compared to WT donor T cells in both B6 to BALB/c model of GVHD(P