Antigen-experienced T cells from immune donors respond to MCMV infection during GVHD and confer protection from CMV disease. DBA/2 (GVHD) were transplanted with BALB/c BM (5 × 10⁶) and CD3⁺ T cells (2.5 × 10⁶) from either naive or MCMV immune donors (latently infected mice). Mice were infected with 5 × 10³ pfu MCMV 4 weeks posttransplant and assessed for CD8⁺ T-cell responses (day 6 PI), viral titers, and liver function (day 6 and 7 PI). (A) Representative plots depicting the expression of PD1 and IE1-tetramer binding by splenic and liver CD8⁺ T cells from GVHD mice that received polyclonal T cells from either naive or MCMV immune donors. (B) Number of MCMV-specific IE1⁺CD8⁺ T cells in spleen and liver, (C) mean fluorescence of PD1 expression on MCMV-specific IE1⁺CD8⁺ T cells in spleen and liver, (D) viral loads in the liver (< 10² pfu represents limit of detection), and (E) liver function assessed by measuring plasma concentration of ALT, AST, and bilirubin are shown. Liver disease was further assessed by histologic analysis. (F) H&E staining of liver sections. (G) Hepatic necrosis scores (see “Materials and Methods”) and (H) numbers of CMV inclusions are shown. Data are pooled from 2 independent experiments (11-12 mice per group). *P = .01-.05; **P = .001-.01; ***P = .0001-.001; ****P < .0001.