In the skin, we found that LCs instructed local T cell pathogenicity in 3 independent models of GVHD following MHC-matched, minor antigen–mismatched transplantation (in both CD8+ and CD4+ T cell–dependent models of GVHD following F→M BMT, and following B6→129 BMT), thus overriding their steady-state role in promoting tolerance (38). Here, CD8A is linked to graft versus host disease.