Contribution of B7RP‐1/ICOS co‐stimulation to lethal acute GVHD

Fujimura J, Takeda K, Kaduka Y, Saito M, Akiba H, Yagita H, Yamashiro Y, Shimizu T, Okumura K. Contribution of B7RP‐1/ICOS co‐stimulation to lethal acute GVHD.
Pediatr Transplantation 2010: 14:540–548. © 2010 John Wiley & Sons A/S. Abstract: Co‐stimulatory molecules expressed on T cells critically regulate donor T‐cell activation and are implicated in acute GVHD after allogeneic BMT. We here investigated the role of interaction between B7‐related protein‐1 (B7RP‐1) and ICOS in murine acute GVHD model that received T cell‐depleted BM cells and splenocytes. Administration of blocking anti‐B7RP‐1 mAb significantly reduced the lethality and symptoms in acute GVHD. A significant hypo‐responsiveness of splenocytes to host alloantigen was observed in the recipient mice treated with anti‐B7RP‐1 mAb. Moreover, acute GVHD was significantly reduced in the recipients of T cells composed of ICOS‐deficient CD8 T cells and WT CD4 T cells compared with that in the recipients of T cells composed of WT CD8 T cells and ICOS‐deficient CD4 T cells. These results suggested that B7RP‐1/ICOS co‐stimulatory signal plays a role in the activation of alloantigen‐reactive donor T cells, particularly in CD8 T cells, in murine acute GVHD model, and that the blockade of B7RP‐1/ICOS interaction may be useful for selectively manipulating allo‐reactive T cells in the recipients with acute GVHD.