We appreciate the comments of Seth et al. (1), because they provide an important finding that is supplementary to our paper (2). They show that recipient mice deficient in CD155 (Cd155−/− mice), a ligand for DNAM-1 (DNAX accessory molecule-1, CD226), exhibited shorter rather than longer survival than WT mice after bone marrow transplantation (BMT) with full MHC disparity. They also show that donor CD4+, but not CD8+, T cells were responsible for the poor survival of the recipient Cd155−/− mice, suggesting that the interaction of CD155 on recipient organs with the receptor ligand on donor CD4+ T cells protects recipient mice from lethal disease after BMT. This observation does not necessarily contradict our findings that DNAM-1 on donor CD8+ T cells is involved in the exacerbation of acute graft-versus-host disease (GVHD) (2). Importantly, CD4+ T cells express TIGIT (T cell immunoreceptor with Ig and ITIM domains), which is another receptor ligand for CD155 that mediates an inhibitory signal in T cells through interaction with CD155 on antigen-presenting cells (3). The binding affinity of TIGIT for CD155 is higher than that of DNAM-1 (3). Thus, one possible explanation for the findings of Seth et al. (1) is that CD4+ T cells might be led out of negative control by TIGIT, resulting in acceleration of alloreactive CD4+ T-cell priming and activation. As shown in our paper (2), DNAM-1 is involved in acute GVHD mediated by CD8+, but not CD4+, T cells. Therefore, this may be the reason why anti–DNAM-1 neutralizing antibody had no effect on the survival of Cd155−/− mice, even when DNAM-1 was bound to CD112 on the recipient organs.