Variation of GVHD severity in MHC-matched mice. (A–C) Survival and percent weight change after lethal irradiation and transplantation of 3,000 Thy-1loLin–Sca-1+c-Kit+ HSC, alone or with whole splenocytes. Recipients of purified HSC grafts did not develop signs of GVHD. B10.BR recipients of AKR/J HSC plus splenocytes recovered to within 5% of baseline weight but did not display overt signs of GVHD, and all mice survived to day 60. In contrast, transplantation of HSC plus splenocytes into irradiated BALB.B and BALB.K mice from B6 and AKR/J donors, respectively, resulted in lethal GVHD that was particularly aggressive in the latter, with a median survival time of 9 days (P = 0.003, compared with B10.BR mice given AKR/J HSC plus splenocytes). (D and E) Liver, terminal ileum, and skin were obtained from surviving B10.BR mice on day 60 for pathology assessment. Significant pathologic evidence of GVHD with a median score of 2 was limited to liver of B10.BR mice given HSC plus splenocytes (P = 0.008, compared with mice given HSC alone), the histology of which revealed portal lymphoid infiltrates and focal bile duct invasion (arrowheads in E) without biliary ductal regeneration.