Liver toxicity caused by AAV capsid-specific CD8+ T cells. Circulating liver enzyme (AST and ALT) levels in Rag-1 −/− BALB/c mice were measured in serum collected 7 days after adoptive transfer of CD8+ T cells (as outlined in Figure 4A: AAV capsid-specific, cap-CD8; control cells, con-CD8; or no cells; n = 4 per experimental group). (A) AAV2. (B) AAV2(Y-F). Data are average ± SD. *P < .05; **P < .01 using Student t test (comparison between mice treated with cap-CD8 and con-CD8). (C) Liver cryosections were generated for the same day-7 time point. Antibody stains show CD8+ T cells (green) and hF.IX+ hepatocytes (red). Representative examples at the indicated original magnification are shown for mice having received cap-CD8 cells and the following vector capsid: AAV2 (upper panels); AAV2(Y-F) (lower left panel); day 28 after AAV2 vector administration (lower right panel). Arrows depict CD8+ cells. Original magnifications are as indicated for each panel.