Central memory gene-modified lymphocytes cultured with IL-7/IL-15 are highly alloreactive. NOD/Scid mice that received a transplant of human skin, and were conditioned with anti-NK antibodies and sublethal irradiation were infused intravenously with TK⁺ lymphocytes or PBLs. (A) Two to 3 weeks after infusion, transplanted human skins were excised from killed mice and analyzed after staining with hematoxylin and eosin (×10 top low, ×40 middle low). Samples were simultaneously analyzed by immunohistochemistry after counterstaining with monoclonal anti-hCD3 antibodies and peroxidase-conjugated second-step reagent (×40 bottom low). Sections from representative animals of 7 independent experiments are shown. (B) Pathological grading of transplanted human skin was performed on the basis of criteria currently used for pathological diagnosis of skin GVHD in patients who underwent transplantation. Frequency of severe skin GVHD (more than grade 2) in 7 independent experiments with 9 independent T-cell donors is shown; baCD3/CD28⁺ IL-7/IL-15 (■, n = 9), baCD3/CD28⁺ IL-7 (, n = 4), baCD3/CD28⁺ IL-2 (, n = 7), aCD3⁺ IL-2 (□, n = 5), or PBLs (, n = 7). *P < .05; **P < .01.